Liquid dispenser with manifold mount for modular independently-actuated pipette channels

ABSTRACT

Automated pipetting systems and methods are disclosed for aspirating and dispensing fluids, particularly biological samples. In one aspect, a liquid dispenser includes a manifold and one or more pipette channels. The manifold includes a vacuum channel, a pressure channel, and a plurality of lanes. Each lane includes an electrical connector, a port to the pressure channel, and a port to the vacuum channel. The pipette channels can be modular. Each pipette channel includes a single dispense head and can be selectively and independently coupled to any one lane of the plurality of lanes. In some aspects, a valve in the pipette channel is in simultaneous fluid communication with a pressure port and a vacuum port of the manifold. The valve selectively diverts gas under pressure and gas under vacuum to the dispense head in response to control signals received through the electrical connector of the manifold.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/340,296, filed May 23, 2016, and U.S. Provisional Application No.62/409,695, filed Oct. 18, 2016, which are hereby incorporated byreference in their entirety.

BACKGROUND Field

The technology described herein generally relates to systems and methodsfor controlling fluid processing operations associated with liquiddispense operations of fluids including samples, particularly multiplebiological samples. The technology relates to automated pipettingsystems to carry out various aspirate and dispense operations.

Description of the Related Art

Diagnostic testing of biological samples is instrumental in the healthcare industry's efforts to quickly and effectively diagnose and treatdisease. Clinical laboratories that perform such diagnostic testingalready receive hundreds or thousands of samples on a daily basis withan ever increasing demand. The challenge of managing such largequantities of samples has been assisted by the automation of sampleanalysis. Automated sample analysis is typically performed by automatedanalyzers that are commonly self-contained systems which performmultistep processes on the biological samples to obtain diagnosticresults.

Understanding that sample flow breaks down into several key steps, itwould be desirable to consider ways to automate as many of these aspossible. For example, a biological sample, once extracted from apatient, must be put in a form suitable for a processing regime. In somecases, the processing regime involves DNA amplification, usingpolymerase chain reaction (PCR) or another suitable technique, toamplify a vector of interest. Clinical laboratories also have differentautomated clinical analyzers performing different processing regimes.Thus, there is a need to prepare samples for diagnostic testing with auniversal liquid handling system that can be easily customized andimplemented in different types of analyzers.

Sample preparation is labor intensive in part because of the number ofliquids, such as reagents, that are required, and the need for multipleliquid transfer (e.g., pipetting) operations. Thus, there is a need foran automated pipetting apparatus, particularly one that can operate onmultiple samples in parallel.

The discussion of the background herein is included to explain thecontext of the inventions described herein. This is not to be taken asan admission that any of the material referred to was published, known,or part of the common general knowledge as of the priority date of anyof the claims.

Throughout the description and claims of the specification the word“comprise” and variations thereof, such as “comprising” and “comprises,”is not intended to exclude other additives, components, integers orsteps.

SUMMARY

A liquid dispenser described herein includes a manifold comprising apressure channel, a vacuum channel, a plurality of pressurecross-channels, each pressure cross-channel beginning at the pressurechannel and terminating at an external surface of the manifold, aplurality of vacuum cross-channels, each vacuum cross-channel beginningat the vacuum channel and terminating at the external surface of themanifold. The liquid dispenser includes one or more pipette channelscoupled to the manifold, each pipette channel comprising a dispensehead, a pressure port configured to receive gas under pressure from onepressure cross-channel, a vacuum port configured to receive gas undervacuum from one vacuum cross-channel, and a valve in simultaneous fluidcommunication with the pressure port and the vacuum port, the valveoperable to selectively divert gas under pressure and gas under vacuumto the dispense head. The liquid dispenser includes electricalconnections configured to transmit control signals from the manifold tothe one or more pipette channels, operation of each valve regulatedindependently of any other valve by the control signals transmitted fromthe manifold.

In some embodiments, each of the one or more pipette channels areselectively and independently coupled to the manifold. In someembodiments, for each pipette channel, the dispense head is coupled to apipette tip, wherein the dispense head is configured to aspirate aliquid into the pipette tip when the valve diverts gas under vacuum tothe dispense head, and wherein the dispense head is configured todispense a liquid from the pipette tip when the valve diverts gas underpressure to the dispense head. In some embodiments, each pipette channelcomprises a single dispense head. In some embodiments, each valve isconfigured to selectively distribute gas under pressure and gas undervacuum from the pressure port and the vacuum port, respectively, to thesingle dispense head. In some embodiments, each pipette channelcomprises a first portion that does not move relative to the manifoldwhen the pipette channel is coupled to the manifold and a second portionthat moves relative to the manifold when the pipette channel is coupledto the manifold. In some embodiments, the valve is enclosed within thefirst portion, the dispense head is coupled to the second portion, and atube connecting the valve and the dispense head is configured to movewithin the first portion when the second portion moves relative to thefirst portion. In some embodiments, the pressure channel comprises afirst end and a second end terminating at an inlet pressure port,wherein the inlet pressure port is connected to an external source ofgas under pressure, wherein the vacuum channel comprises a first end anda second end terminating at an inlet vacuum port, and wherein the inletvacuum port is connected to an external source of gas under vacuum. Insome embodiments, the manifold only accepts gas under pressure and gasunder vacuum through the inlet pressure port and the inlet vacuum port,respectively. In some embodiments, the electrical connections arefurther configured to transmit electrical signals from the manifold tothe one or more pipette channels, each pipette channel poweredindependently of any pipette channel by the electrical signalstransmitted from the manifold. In some embodiments, each of the one ormore pipette channels only receives control signals and electricalsignals through the electrical connection with the manifold. In someembodiments, each valve is a three way solenoid valve. In someembodiments, each valve is a low pressure solenoid valve. In someembodiments, each valve is a solenoid valve rated for less than 10 psi.In some embodiments, at least one pipette channel further comprises amagnetic brake. In some embodiments, the magnetic brake is configured toreduce free-fall of the dispense head of the at least one pipettechannel in the event of loss of electrical signals from the manifold. Insome embodiments, at least one pipette channel further comprises a ballscrew configured to move the dispense head of the at least one pipettechannel in a vertical direction relative to the manifold. In someembodiments, the at least one pipette channel further comprises acoupling configured to reduce misalignment of the ball screw. In someembodiments, gas provided by each pressure cross-channel to the pressureport of the respective pipette channel is at the same pressure as gasprovided by each other pressure cross-channel of the plurality ofpressure cross-channels. In some embodiments, the manifold furthercomprises a second pressure channel comprising a plurality of pressurecross-channels, wherein the pressure port of each of a first pluralityof pipette channels is coupled to one pressure cross-channel of thefirst pressure channel, wherein the pressure port of each of a second,different plurality of pipette channels is coupled to one pressurecross-channel of the second pressure channel, and wherein the manifoldprovides gas under pressure to the first plurality of pipette channelsat a first pressure and simultaneously provides gas to the secondplurality of pipette channels at a second, different pressure. In someembodiments, each pipette channel is configured to be selectivelymounted to the manifold with two screws. In some embodiments, the twoscrews are captive to the pipette channel. In some embodiments, at leastone pipette channel comprises one or more pegs configured to align withone or more openings of the manifold. In some embodiments, the one ormore pegs engage the one or more openings in the manifold before anelectrical connector on the pipette channel and an electrical connectoron the manifold engage. In some embodiments, each pipette channelcomprises one or more o-rings configured to provide a seal between eachpipette channel and the manifold. In some embodiments, the one or moreo-rings are captured in a dove-tail groove in each pipette channel. Insome embodiments, the liquid dispenser includes a first pipette channeland a second pipette channel coupled to the manifold, wherein the firstpipette channel comprises a different calibration setting fordispensing. In some embodiments, two or more pipette channels havedifferent dispense heads. In some embodiments, one pressurecross-channel and one vacuum cross-channel are not coupled to a pipettechannel, and wherein the liquid dispenser further comprises a blankingplate configured to close the one pressure cross-channel and the onevacuum cross-channel of the manifold that are not coupled to a pipettechannel. In some embodiments, the pressure channel and the vacuumchannel are physically and fluidically isolated from each other withinthe manifold. In some embodiments, the manifold comprises a singlepressure channel and a single vacuum channel. In some embodiments, foreach pipette channel, the valve is configured to be in simultaneousfluid communication with the pressure channel and the vacuum channel ofthe manifold, the valve operable to selectively divert gas underpressure and gas under vacuum to the dispense head. In some embodiments,each pipette channel further comprises a tube, the tube having a firstend terminating at the valve and a second end terminating at thedispense head, wherein the tube is configured to direct gas from thevalve to the dispense head. In some embodiments, the tube is the onlypneumatic connection between the valve and the dispense head. In someembodiments, the tube is configured to bend as the dispense head movesvertically relative to the manifold. In some embodiments, the tube isenclosed by an outer housing of the pipette channel. In someembodiments, for each pipette channel, the valve does not move relativeto the manifold when the dispense head moves relative to the manifold.In some embodiments, each pipette channel further comprises a secondvalve that moves with the dispense head relative to the manifold. Insome embodiments, operation of each second valve is regulatedindependently of any other second valve by control signals transmittedfrom the manifold. In some embodiments, the second valve is configuredto control the aspirate and dispense operations of the dispense head. Insome embodiments, the second valve is a solenoid valve. In someembodiments, the dispense head performs an aspirate operation when thevalve diverts gas under vacuum to the dispense head, wherein thedispense head performs a dispense operation when the valve diverts gasunder pressure to the dispense head, and wherein the second valve isconfigured to control a volume of a liquid aspirated and dispensed bythe dispense head during aspirate and dispense operations, respectively.In some embodiments, the dispense head performs an aspirate operationwhen the valve diverts gas under vacuum to the dispense head, whereinthe dispense head performs a dispense operation when the valve divertsgas under pressure to the dispense head, and wherein the second valve isconfigured to control a timing of the aspirate operation and thedispense operation. In some embodiments, each second valve is poweredindependently of any other second valve by the electrical signalstransmitted from the manifold. In some embodiments, each pipette channelis configured to be coupled and uncoupled from the manifoldindependently of another pipette channel coupled to the manifold. Insome embodiments, each dispense head is moveable along a verticaldirection relative to the manifold independently of another dispensehead coupled to the manifold. In some embodiments, each of the one ormore pipette channels is modular. In some embodiments, the one or morepipette channels comprise a first pipette channel and a second pipettechannel coupled to the manifold, wherein the first pipette channel iscalibrated at a first setting related to volume for aspirate anddispense operations and the second pipette channel is calibrated at asecond, different setting related to volume for aspirate and dispenseoperations. In some embodiments, the one or more pipette channelscomprise a first pipette channel and a second pipette channel coupled tothe manifold, wherein the first pipette channel is calibrated at a firstsetting related to pressure for aspirate and dispense operations and thesecond pipette channel is calibrated at a second, different settingrelated to pressure for aspirate and dispense operations. In someembodiments, the first pipette channel and the second pipette channelare calibrated before the first pipette channel and the second pipettechannel are coupled to the manifold. In some embodiments, the one ormore pipette channels comprise a first pipette channel and a secondpipette channel, wherein the pressure port and the vacuum port of thefirst pipette channel have the same orientation as the pressure port andthe vacuum port of the second pipette channel. In some embodiments, thefirst pipette channel and the second pipette channel have one or moredifferent dimensions. In some embodiments, the first pipette channel andthe second pipette channel are configured to perform different functionssimultaneously. In some embodiments, the liquid dispenser has 3 pipettechannels coupled to the manifold. In some embodiments, the liquiddispenser has 5 pipette channels coupled to the manifold. In someembodiments, each pipette channel comprises a pipette tip sensorconfigured to detect whether a pipette tip is engaged with the dispensehead. In some embodiments, each pipette channel comprises a sensorconfigured to sense when vertical motion of the dispense head isobstructed. In some embodiments, the one or more pipette channelscomprise two or more pipette channels, wherein each valve of the two ormore pipette channels is configured to be individually actuated toselectively divert the gas under pressure or the gas under vacuum fromthe manifold to each dispense head.

A method of dispensing and aspirating a fluid is provided herein. Themethod includes: providing a manifold comprising a vacuum channel and apressure channel; providing one or more pipette channels, each pipettechannel comprising a dispense head, a vacuum port, a pressure port, andan independently controlled valve in simultaneous fluid communicationwith the vacuum port and the pressure port; selectively engaging the oneor more pipette channels to the manifold, wherein selectively engagingcomprises connecting each vacuum port of the one or more pipettechannels to the vacuum channel of the manifold and connecting eachpressure port of the one or more pipette channels to the pressurechannel of the manifold; transmitting control signals from the manifoldto a first pipette channel of the one or more pipette channels toindependently control operation of the independently controlled valve toselectively direct gas under vacuum or gas under pressure receivedthrough the vacuum port and the pressure port of the first pipettechannel to the dispense head of the first pipette channel; andperforming aspirate and dispense operations with the first pipettechannel, the aspirate and dispense operations comprising aspirating thefluid or dispensing the fluid in response to receipt of gas under vacuumor gas under pressure, respectively, in the dispense head of the firstpipette channel from the independently controlled valve of the firstpipette channel.

In some embodiments, the method includes selectively engaging the firstpipette channel and a second pipette channel to the manifold;transmitting control signals from the manifold to the second pipettechannel to independently control operation of the independentlycontrolled valve to selectively direct gas under vacuum or gas underpressure received through the vacuum port and the pressure port of thesecond pipette channel to the dispense head of the second pipettechannel; and performing aspirate and dispense operations with the secondpipette channel, the aspirate and dispense operations comprisingaspirating a second fluid or dispensing a second fluid in response toreceipt of gas under vacuum or gas under pressure, respectively, in thedispense head of the second pipette channel from the independentlycontrolled valve of the second pipette channel. In some embodiments, theaspirate and dispense operations of the first pipette channel and thesecond pipette channel occur simultaneously. In some embodiments, theaspirate and dispense operations of the first pipette channel and thesecond pipette channel occur independently. In some embodiments, thefirst pipette channel dispenses at the same time the second pipettechannel aspirates. In some embodiments, the first pipette channel andthe second pipette channel simultaneously aspirate a different volume offluid. In some embodiments, the first pipette channel and the secondchannel simultaneously dispense a different volume of liquid. In someembodiments, the first pipette channel and the second pipette channelsimultaneously aspirate a volume of fluid at different pressures. Insome embodiments, the first pipette channel and the second channelsimultaneously dispense a volume of fluid at different pressures. Insome embodiments, the independently controlled valve of the firstpipette channel diverts gas under pressure at the same time theindependently controlled valve of the second pipette channel diverts gasunder vacuum. In some embodiments, the independently controlled valve ofthe first pipette channel starts or stops the diversion of gasindependently of the independently controlled valve of the secondpipette channel. In some embodiments, the method includes selectivelyengaging the first pipette channel and a second pipette channel to themanifold, wherein the valve of the first pipette channel diverts gasunder pressure to the dispense head of the first pipette channel at thesame time the valve of the second pipette channel diverts gas undervacuum to the dispense head of the second pipette channel, such that thedispense head of the first pipette channel dispenses a fluid at the sametime the dispense head of the second pipette channel aspirates a fluid.In some embodiments, the pressure channel comprises a plurality ofpressure cross-channels and the vacuum channel comprises a plurality ofvacuum cross-channels, and wherein each pipette channel is configured toconnect to one pressure cross-channel and one vacuum cross-channel whenthe pipette channel is selectively engaged to the manifold. In someembodiments, the manifold comprises a plurality of lanes, each lanecomprising one pressure cross-channel and one vacuum cross channel, andwherein selectively engaging comprises engaging one pipette channel toany one lane of the plurality of lanes. In some embodiments, the methodincludes, in sequence, aspirating the fluid in response to receipt ofgas under vacuum in the dispense head of the first pipette channel anddispensing the fluid in response to receipt of gas under pressure in thedispense head. In some embodiments, the method includes coupling asingle source of gas under pressure and a single source of gas undervacuum to the manifold. In some embodiments, the pressure channelterminates at an inlet pressure port and the vacuum channel terminatesat an inlet vacuum port, wherein the manifold only accepts gas underpressure and gas under vacuum through the inlet pressure port and theinlet vacuum port, respectively. In some embodiments, the pipettechannel only accepts gas under pressure and gas under vacuum through thepressure port and the vacuum port, respectively. In some embodiments,the method includes transmitting electrical signals from the manifold tothe one or more pipette channels, each pipette channel poweredindependently of any pipette channel by the electrical signalstransmitted from the manifold. In some embodiments, each of the one ormore pipette channels only receives control signals and electricalsignals through the electrical connection with the manifold. In someembodiments, the method includes reducing free-fall of the dispense headin the event of loss of electrical signals via a magnetic brake. In someembodiments, selectively engaging the first pipette channel with themanifold comprises aligning one or more pegs of the pipette channel withone or more openings of the manifold. In some embodiments, selectivelyengaging the first pipette channel with the manifold comprisestightening one or more captive screws of the pipette channel. In someembodiments, selectively engaging the first pipette channel with themanifold comprises compressing a seal between the first pipette channeland the manifold. In some embodiments, the seal is a captive o-ring ofthe pipette channel. In some embodiments, the method includesselectively directing gas under pressure and gas under vacuum receivedthrough the pressure port and the vacuum port of the first pipettechannel to the dispense head of the first pipette channel via a tube. Insome embodiments, the tube is the only pneumatic connection between thevalve and the dispense head. In some embodiments, the tube is configuredto bend as the dispense head moves vertically. In some embodiments, thefluid comprises a liquid. In some embodiments, the fluid comprises agas.

A liquid dispenser described herein includes a manifold comprising avacuum channel, a pressure channel, and a plurality of lanes, each lanecomprising an electrical connector, a port to the pressure channel, anda port to the vacuum channel; and one or more pipette channels, eachpipette channel comprising a single dispense head and configured tocouple to the electrical connector, the pressure port, and the vacuumport of any one lane of the plurality of lanes.

In some embodiments, each pipette channel comprises a valve configuredto selectively distribute gas under pressure and gas under vacuum fromthe pressure port and the vacuum port, respectively, to the singledispense head. In some embodiments, each of the one or more pipettechannels are coupled to one lane of the plurality of lanes, and wherein,for each pipette channel, operation of the valve is independentlycontrolled by signals transmitted to the valve via the electricalconnector of the one lane to which the pipette channel is coupled. Insome embodiments, each pipette channel comprises a first portion thatdoes not move relative to the manifold when the pipette channel iscoupled to the manifold and a second portion that moves relative to themanifold when the pipette channel is coupled to the manifold. In someembodiments, the valve is enclosed within the first portion, thedispense head is coupled to the second portion, and a tube connectingthe valve and the dispense head is configured to move within the firstportion when the second portion moves relative to the first portion. Insome embodiments, each pipette channel comprises an electricalconnector, a pressure port, and a vacuum port. In some embodiments, theelectrical connector, the pressure port, and the vacuum port of anypipette channel is configured to couple to the electrical connector, thepressure port, and the vacuum port, respectively, of any one lane of theplurality of lanes. In some embodiments, the electrical connector, thepressure port, and the vacuum port of the one or more pipette channelsdo not move relative to the manifold when the electrical connector, thepressure port, and the vacuum port of the one or more pipettes channelsare coupled to the manifold. In some embodiments, the single dispensehead of the one or more pipette channels moves relative to the manifoldwhen the one or more pipettes channels are coupled to the manifold. Insome embodiments, the liquid dispenser includes a plurality of pipettechannels, wherein each lane of the plurality of lanes is configured tocouple to any one pipette channel of the plurality of pipette channels.In some embodiments, the pressure channel and the vacuum channel arephysically and fluidically isolated from each other within the manifold.In some embodiments, the manifold comprises a single pressure channeland a single vacuum channel. In some embodiments, each pipette channelis configured to selectively couple and uncouple to the electricalconnector, the pressure port, and the vacuum port of any one lane of theplurality of lanes. In some embodiments, a longitudinal axis of eachlane of the plurality of lanes is oriented transverse to the pressurechannel. In some embodiments, a longitudinal axis of each lane of theplurality of lanes is oriented transverse to the vacuum channel. In someembodiments, the one or more pipette channels comprise a plurality ofpipette channels, wherein at least one pipette channel of the pluralityof pipette channels is coupled to one lane of the plurality of lanes,and wherein at least one lane of the plurality of lanes is not coupledto a pipette channel of the plurality of pipette channels. In someembodiments, the liquid dispenser includes a cover configured to sealthe pressure port and the vacuum port of the at least one lane that isnot coupled to a pipette channel of the plurality of pipette channels.In some embodiments, the liquid dispenser includes only one pipettechannel, wherein the pipette channel is coupled to one lane of theplurality of lanes, and wherein each of the remaining lanes of theplurality of lanes is not coupled to a pipette channel. In someembodiments, each lane comprises a single port to the pressure channeland a single port to the vacuum channel. In some embodiments, the liquiddispenser includes a first pipette channel coupled to a first lane ofthe plurality of lanes and a second pipette channel coupled to a secondlane of the plurality of lanes, wherein the single dispense head of thefirst pipette channel aspirates a fluid at the same time the singledispense head of the second pipette channel dispenses a fluid. In someembodiments, the one or more pipette channels comprises two pipettechannels with different calibration settings related to pressure of gasin the dispense head during aspirate and dispense operations. In someembodiments, the one or more pipette channels comprises two pipettechannels with different calibration settings related to volume of fluidaspirated and dispensed during aspirate and dispense operations. In someembodiments, the one or more pipette channels comprises two pipettechannels with different calibration settings related to speed ofaspirate and dispense operations. In some embodiments, the one or morepipette channels comprise a plurality of pipette channels, wherein atleast two of the plurality of pipette channels are identical. In someembodiments, the one or more pipette channels comprise a plurality ofpipette channels, wherein at least two of the plurality of pipettechannels are different. In some embodiments, the at least two differentpipette channels have one or more different dimensions. In someembodiments, each pipette channel comprises a valve operable to controlthe flow of gas within each pipette channel. In some embodiments, eachpipette channel comprises a valve operable to control the aspirate anddispense operations of the single dispense head of the pipette channel.In some embodiments, each of the one or more pipette channels areselectively and independently coupled to the manifold. In someembodiments, the pressure channel comprises a first end and a second endterminating at an inlet pressure port, wherein the inlet pressure portis connected to an external source of gas under pressure, wherein thevacuum channel comprises a first end and a second end terminating at aninlet vacuum port, and wherein the inlet vacuum port is connected to anexternal source of gas under vacuum. In some embodiments, the manifoldonly accepts gas under pressure and gas under vacuum through the inletpressure port and the inlet vacuum port, respectively. In someembodiments, the electrical connector of each lane of the plurality oflanes is configured to transmit electrical signals from the manifold toone pipette channel, and wherein each pipette channel is configured,when coupled to the manifold, to be powered independently of any otherpipette channel coupled to the manifold by the electrical signalstransmitted from the manifold. In some embodiments, each of the one ormore pipette channels is coupled to the manifold, and wherein each ofthe one or more pipette channels only receives control signals andelectrical signals through the electrical connector of the lane to whichthe respective pipette channel is coupled. In some embodiments, at leastone pipette channel further comprises a magnetic brake. In someembodiments, the magnetic brake of the at least one pipette channel isconfigured to reduce free-fall of the single dispense head of the atleast one pipette channel in the event of loss of electrical signals. Insome embodiments, at least one pipette channel further comprises a ballscrew configured to move the single dispense head of the at least onepipette channel in a vertical direction relative to the manifold. Insome embodiments, the at least one pipette channel further comprises acoupling configured to reduce misalignment of the ball screw. In someembodiments, the liquid dispenser includes a plurality of pipettechannels coupled to the manifold, and the pressure channel provides gasunder pressure to all pipette channels coupled to the manifold at thesame pressure. In some embodiments, the liquid dispenser includes aplurality of pipette channels coupled to the manifold, and the vacuumchannel provides gas under vacuum to all pipette channels coupled to themanifold at the same pressure. In some embodiments, the liquid dispenserincludes a plurality of pipette channels coupled to the manifold, andthe manifold is operable to provide gas under pressure to a first set ofpipette channels at a first pressure and to simultaneously provide gasto a second, different set of pipette channels at a second, differentpressure. In some embodiments, each pipette channel is configured to beselectively mounted to the manifold with two screws. In someembodiments, the two screws are captive to the pipette channel. In someembodiments, at least one pipette channel comprises one or more pegsconfigured to align with one or more openings of the manifold. In someembodiments, the one or more pegs engage the one or more openings of themanifold before an electrical connector engages the pipette channel. Insome embodiments, each pipette channel comprises one or more o-ringsconfigured to provide a seal between each pipette channel and themanifold. In some embodiments, the one or more o-rings are captured in adove-tail groove in each pipette channel. In some embodiments, the oneor more pipette channels comprises a first pipette channel and a secondpipette channel coupled to the manifold. In some embodiments, the firstpipette channel comprises a different calibration setting for dispensingthan the second pipette channel. In some embodiments, the first pipettechannel and the second pipette channel have different dispense heads. Insome embodiments, the liquid dispenser includes a blanking plateconfigured to close one port to the pressure channel and one port to thevacuum channel of the manifold. In some embodiments, each pipettechannel comprises a valve configured to selectively distribute gas undervacuum and gas under pressure from the vacuum port and the pressureport, respectively, to the single dispense head, wherein each pipettechannel further comprises a tube, the tube having a first endterminating at the valve and a second end terminating at the dispensehead, and wherein the tube is configured to divert gas from the valve tothe dispense head. In some embodiments, the tube is the only pneumaticconnection between the valve and the dispense head. In some embodiments,the tube is configured to bend as the dispense head moves verticallyrelative to the manifold when the pipette channel is coupled to themanifold. In some embodiments, the valve does not move verticallyrelative to the manifold when the pipette channel is coupled to themanifold, and wherein the tube is configured to bend within a housing ofthe pipette channel when the dispense head moves vertically relative tothe manifold. In some embodiments, the tube and the valve are enclosedwithin a first housing of the pipette channel and the dispense head iscoupled to a second housing of the pipette channel enclosing a secondvalve. In some embodiments, the tube is enclosed within an outer housingof the pipette channel. In some embodiments, each pipette channelcomprises a valve configured to selectively distribute gas under vacuumand gas under pressure from the vacuum port and the pressure port,respectively, to the single dispense head, and wherein each pipettechannel further comprises a second valve that is configured to move withthe dispense head when the pipette channel is coupled to the manifold.In some embodiments, operation of each second valve is regulatedindependently of any other second valve by control signals transmittedfrom the manifold. In some embodiments, the second valve is configuredto control the aspirate and dispense operations of the dispense head. Insome embodiments, the second valve is a solenoid valve. In someembodiments, the second valve is configured to control the amount ofliquid aspirated or dispensed by the dispense head. In some embodiments,the second valve is configured to control the timing of liquid aspiratedor dispensed by the dispense head. In some embodiments, each secondvalve is powered independently of any second valve by the electricalsignals transmitted from the manifold. In some embodiments, each pipettechannel comprises a valve configured to selectively distribute gas underpressure and gas under vacuum from the pressure port and the vacuumport, respectively, to the single dispense head, and wherein each valveis a three way solenoid valve. In some embodiments, each pipette channelis configured to be coupled and uncoupled from the manifoldindependently of another pipette channel coupled to the manifold. Insome embodiments, the one or more pipette channels comprises a pluralityof pipette channels coupled to the manifold, wherein each dispense headof the plurality of pipette channels is moveable along a verticaldirection relative to the manifold independently of another dispensehead coupled to the manifold. In some embodiments, the one or morepipette channels are modular. In some embodiments, the one or morepipette channels comprises a plurality of identical pipette channels. Insome embodiments, the one or more pipette channels comprises a firstpipette channel and a second pipette channel coupled to the manifold,wherein the first pipette channel and the second pipette channel arecalibrated to aspirate and dispense a volume of liquid, and wherein thefirst pipette channel comprises a volume calibration setting that isdifferent than the volume calibration setting of the second pipettechannel. In some embodiments, the one or more pipette channel comprisesa first pipette channel and a second pipette channel coupled to themanifold, wherein the first pipette channel and the second pipettechannel are calibrated to aspirate and dispense a liquid at a pressure,and wherein the first pipette channel comprises a pressure calibrationsetting that is different than the pressure calibration setting of thesecond pipette channel. In some embodiments, the one or more pipettechannel comprises a first pipette channel and a second pipette channeleach comprising a pressure port and a vacuum port, and wherein thepressure port and the vacuum port of the first pipette channel have thesame orientation of as the pressure port and the vacuum port of thesecond pipette channel. In some embodiments, the first pipette channeland the second pipette channel have one or more different dimensions. Insome embodiments, the first pipette channel and the second pipettechannel perform different functions simultaneously. In some embodiments,the liquid dispenser has 3 pipette channels coupled to the manifold. Insome embodiments, the liquid dispenser has 5 pipette channels coupled tothe manifold. In some embodiments, each dispense head is independentlymovable in a vertical direction relative to the manifold when thedispense head is coupled to the manifold via its respective pipettechannel. In some embodiments, each pipette channel comprises a pipettetip sensor configured to detect whether a pipette tip is engaged withthe dispense head. In some embodiments, each pipette channel comprises asensor configured to sense when vertical motion of the dispense head isobstructed. In some embodiments, the liquid dispenser includes two ormore pipette channels coupled to the manifold, wherein each valve of thetwo or more pipette channels is configured to be individually actuatedto selectively divert gas under vacuum or gas under pressure from themanifold to each dispense head.

A system described herein includes a manifold comprising a pressurechannel, a vacuum channel, one pressure sub-channel beginning at thepressure channel and terminating at an external surface of the manifold,one vacuum sub-channel beginning at the vacuum channel and terminatingat the external surface of the manifold. The system includes one pipettechannel coupled to the manifold, the pipette channel comprising a singledispense head, a pressure port configured to receive gas under pressurefrom the pressure sub-channel of the manifold, a vacuum port configuredto receive gas under vacuum from the vacuum sub-channel of the manifold,and a valve in simultaneous fluid communication with the pressure portand the vacuum port, the valve operable to selectively divert gas underpressure and gas under vacuum to the dispense head. The system includeselectrical connections configured to transmit control signals from themanifold to the pipette channel, operation of the valve regulatedexclusively by the control signals transmitted from the manifold.

In some embodiments, the system includes a second pipette channel thatis not coupled to the manifold, wherein the second pipette channel isidentical to the pipette channel coupled to the manifold. In someembodiments, the system includes a second pipette channel that is notcoupled to the manifold, wherein the second pipette channel is differentthan the pipette channel coupled to the manifold.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a schematic figure of an embodiment of a liquid dispenseraccording to a first embodiment.

FIGS. 1B-4 show views of a liquid dispenser according to a secondembodiment.

FIGS. 5-34D show views of a liquid dispenser according to a thirdembodiment.

FIGS. 35-55 show views of a liquid dispenser according to a fourthembodiment.

FIGS. 56-57 show views of a liquid dispenser according to a fifthembodiment.

FIGS. 58-60 show views of the third embodiment.

FIGS. 61-64 show views of the fourth embodiment.

FIGS. 65A-65B show views of a manifold.

DETAILED DESCRIPTION

Any feature or combination of features described herein are includedwithin the scope of the present disclosure provided that the featuresincluded in any such combination are not mutually inconsistent as willbe apparent from the context, this description, and the knowledge of oneskilled in the art. In addition, any feature or combination of featuresmay be specifically excluded from any embodiment of the presentdisclosure. For purposes of summarizing the present disclosure, certainaspects, advantages, and novel features of the present disclosure aredescribed herein. Of course, it is to be understood that not necessarilyall such aspects, advantages, or features will be present in anyparticular embodiment of the present disclosure.

It is to be understood that embodiments presented herein are by way ofexample and not by way of limitation. The intent of the followingdetailed description, although discussing exemplary embodiments, is tobe construed to cover all modifications, alternatives, and equivalentsof the embodiments as may fall within the spirit and scope of thepresent disclosure.

FIG. 1A is a schematic figure of an embodiment of a liquid dispenser 1according to embodiments of the present disclosure. FIG. 1A is aschematic figure, not drawn to scale. The liquid dispenser 1 includes amanifold 2 having a pressure channel 4 to deliver gas under pressure anda vacuum channel 5 to deliver gas under vacuum. The manifold 2 includesa plurality of pressure cross-channels 6, each pressure cross-channel 6beginning at the pressure channel 4 and terminating at an externalsurface of the manifold 2 as shown in FIG. 1A. The manifold 2 includes aplurality of vacuum cross-channels 7, each vacuum cross-channel 7beginning at the vacuum channel 5 and terminating at the externalsurface of the manifold 2 as shown in FIG. 1A. The pressure channel 4comprises a first end and a second end terminating at an inlet pressureport 4B. The inlet pressure port is connected to an external source ofgas under pressure. The vacuum channel 5 comprises a first end and asecond end terminating at an inlet vacuum port 5B. The inlet vacuum portis connected to an external source of gas under vacuum. The pressurechannel 4 and the vacuum channel 5B are physically and fluidicallyisolated from each other within the manifold 2. In some implementationsdescribed herein, the end of a pressure cross-channel 6 terminating atthe external surface of the manifold 2 is referred to as a port to thepressure channel 4 and the end of a vacuum cross-channel 7 terminatingat the external surface of the manifold 2 is referred to as a port tothe vacuum channel 5.

The liquid dispenser 1 includes one or more pipette channels. In theillustrated embodiment, the liquid dispenser includes three pipettechannels, pipette channels 8A, 8B, 8C. Each pipette channel is designedto selectively couple to and selectively uncouple from the manifold 2.FIG. 1A illustrates the pipette channels 8A, 8B, 8C before they havebeen selectively coupled to the manifold 2, or after they have beenselectively uncoupled from the manifold 2. Any one pipette channel 8A,8B, and 8C can be selectively coupled and uncoupled to one lane 3 of themanifold 2, independent of the state of any other pipette channel. Eachpipette channel 8A, 8B, 8C includes a dispense head 9 designed toperform dispense and aspirate operations. Each pipette channel 8A, 8B,8C includes a pressure port 10 designed to receive gas under pressurefrom one pressure cross-channel 6. Each pipette channel 8A, 8B, 8Cincludes a vacuum port 11 designed to receive gas under vacuum from onevacuum cross-channel 7. Each pipette channel 8A, 8B, 8C includes a valve12 in simultaneous fluid communication with the pressure port 10 and thevacuum port 11. The valve 12 is operable to selectively divert gas underpressure and gas under vacuum to the dispense head 9. The valve 12 isdesigned to direct gas under pressure to the dispense head. The valve 12is designed to distribute gas under vacuum to the dispense head 9. Thevalve 12 is designed to divert either gas under pressure or gas undervacuum to the dispense head 9, while being simultaneously supplied withgas under pressure and gas under vacuum by the manifold 2. For eachpipette channel 8A, 8B, 8C, the dispense head 9 is coupled to a pipettetip (not shown). The dispense head 9 is designed to dispense a liquidfrom the pipette tip when the valve 12 diverts gas under pressure to thedispense head 9. The dispense head 9 is designed to aspirate a liquidinto the pipette tip when the valve 12 diverts gas under vacuum to thedispense head 9.

The liquid dispenser 1 includes an electrical connector 13 on themanifold 2 designed to transmit control signals from the manifold 2 tothe pipette channels 8A, 8B, 8C. The operation of each valve 12 isregulated independently of any other valve 12 by the control signalstransmitted from the manifold 2. Each independently controllable valve12 is housed in a pipette channel. The independently controllable valves12 selectively divert gas under pressure and gas under vacuum based, atleast in part on, the control signals. Each independently controllablevalve 12 has simultaneous access to the pressure channel 4 and thevacuum channel 5B when the respective pipette channel (pipette channel8A, 8B, or 8C) with the independently controllable valve 12 is coupledto the manifold 2.

As explained above, each of the pipette channels 8A, 8B, 8C areselectively and independently coupled to the manifold 2. In someembodiments, the manifold 2 comprises a plurality of lanes 3, each lane3 comprising one pressure cross-channel 6 and one vacuum cross channel7. Each lane comprises an electrical connector 13. During installation,each pipette channel 8A, 8B, 8C is selective engaged to a lane of theplurality of lanes 3. In some embodiments, each pipette channel 8A, 8B,8C is selectively engaged to any one lane of the plurality of lanes 3.Each pipette channel 8A, 8B, 8C comprises a single dispense head 9. Insome embodiments, each lane 3 can be defined by one or more of thefollowing features: a single pressure cross-channel 6, a single vacuumcross-channel 7, an electrical connector 13, a single pipette channel8A, 8B, 8C, a single dispense head 9 coupled thereto, etc.

FIG. 1A shows a cross-sectional view of the pipette channels 8A, 8B, 8C.Each pipette channel 8A, 8B, 8C includes a corresponding electricalconnector 14. In addition to the control signals, the electricalconnectors 13, 14 are further designed to transmit electrical signalsfrom the manifold 2 to the pipette channels 8A, 8B, 8C. Each pipettechannel 8A, 8B, 8C is powered independently of any other pipette channel8A, 8B, 8C by the electrical signals transmitted from the manifold 2. Insome embodiments, each pipette channel 8A, 8B, 8C includes a cable 15transmitting control signals and electrical signals from the electricalconnector 14 to one or more components of the pipette channel 8A, 8B,8C. In the illustrated embodiment, the cable 15 transmits controlsignals and electrical signals from the electrical connector 14 to thevalve 12. The cable 15 can continue from the valve 12 to the dispensehead 9, or another cable can be used to connect the electrical connector14 to the dispense head 9. Other configurations are contemplated. Thereare many signals that can be transmitted through the electricalconnector 14 of the pipette channels 8A, 8B, 8C. The valve 12 can becontrolled by control signals, but other components can be controlled aswell. In some embodiments, the electrical connector 14 is considered abackplane connector. The electrical connector 14 can be integral to thecircuit board of the pipette channels 8A, 8B, 8C. The valve 12 canconnect to the circuit board such as through one or more cables. Thepipette channels 8A, 8B, 8C can include cables that connect the circuitboard to another circuit board above the dispense head 9. The dispensehead 9 is then connected via another set of cables to this secondcircuit board. The liquid dispenser 1 can include any number of cablesand circuit boards needed to perform the functions described herein.

Each pipette channel 8A, 8B, 8C comprises a tube 16. The tube 16 has afirst end terminating at the valve 12 and a second end terminating atthe dispense head 9. The tube 16 is designed to direct gas from thevalve 12 to the dispense head 9. In some embodiments, the tube 16 tubeis the only pneumatic connection between the valve 12 and the dispensehead 9. The tube 16 is completely enclosed inside an outer housing ofthe pipette channel 8A, 8B, 8C. As shown in FIG. 1A, the tube 16 isdesigned to bend as the dispense head 9 moves vertically. The dispensehead 9 is shown in different vertical positions to illustrate theindependent vertical motion of the dispense head 9 relative to a portionof the pipette channel 8A, 8B, 8C that is engaged to a lane 3. The tube16 bends as needed within the pipette channel 8A, 8B, 8C as the dispensehead 9 travels up and down.

In some cases, such as that shown in FIG. 1A, there are more lanes 3 onthe manifold 2 than there are pipette channels. The system 1 can includeone or more blanking plates, such as blanking plates 17, configured toseal portions of the manifold 2 that are not coupled to a pipettechannel. For example, one blanking plate 17 can be configured to coupleto one lane 3 of the manifold 2 and seal one pressure cross-channel 6and one vacuum cross-channel 7 of the lane 3 to which the blanking plate17 is coupled. The system 1, includes two blanking plates 17, eachconfigured to seal a pressure cross-channel 6 and a vacuum cross-channel7 of one lane 3. When each of the three pipette channels 8A, 8B, and 8Cand each of the two blanking plates 17 are coupled to one lane 3 of themanifold 2, each of the pressure cross-channels 6 and each of the vacuumcross-channels 7 are sealed to the ambient environment. Only the inletpressure port 4B and the inlet vacuum port 5B are open to the ambientenvironment. As explained above, an external source of gas underpressure can be coupled to the manifold 2 at the inlet pressure port 4Band an external source of gas under vacuum can be coupled to themanifold 2 at the inlet vacuum port 5B. In some cases, the system 1 caninclude a blanking plate (not shown) configured to seal pressurecross-channels and vacuum cross-channels of more than one lane.

Embodiments of the valve 12 described herein can include three waysolenoid valve. The valve 12 can include very few parts, with few wearpoints. One non-limiting example valve 12 is a Bullet Valve® by Mac®(part number BV309A-CC1-00 or VC309A-CD1-00). The valve 12 can beimplemented as a 3 Way Normally Closed or a 3 Way Universal valve.Operational benefits of the valve 12 include one or more of thefollowing: a shorter stroke with high shifting forces, balanced poppet,and precise reliability. The valve 12 can be mounted without fasteners.The valve 12 can be immune to pressure fluctuations. The solenoid can beisolated from contaminated air. The valve 12 can be supplied with 12 VDCor 24 VDC voltage. The valve 12 can operate on various fluids, includingcompressed air, vacuum and/or inert gases. The pressure range can befrom vacuum to 120 PSI. The valve 12 can operate as a selector valvewhere gas under pressure comes into the #3 port and gas under vacuumcomes into the #1 port. Although embodiments of the valve 12 aredescribed herein in the context of a three way solenoid valve, othertypes of valves may be implemented.

FIGS. 1B-4 show views of a liquid dispenser 100 according to oneembodiment of the present disclosure. Liquid dispenser 100 comprises amanifold 102 that has a front 104, a back 106, and sides 108. Themanifold 102 is configured to accept one or more pipette channels 110,where each pipette channel 110 houses various components used inaspirate and dispense operations. The pipette channel 110 has a front112, a back 114, and sides 116.

The liquid dispenser 100 is modular, thereby enabling flexibility andversatility in arranging the one or more pipette channels 110 relativeto the manifold 102. In the embodiment shown, the front 112 of thepipette channels 110 includes a pipette module 120. The pipette module120 includes pipetting mechanisms that use air under vacuum andpressurized air to aspirate and dispense fluid from a pipette tip 122.One non-limiting example pipette tip 120 is the Air Driven OEM ChannelPipettor by Seyonic® (part number PCNC-0061-00). Pipette tips 122 can bedisposable. Each pipette module 120 can include a tip adapter 118,wherein each tip adapter 118 is configured to accept a pipette tip 122.A pipette tip 122 can be attached to the tip adapter 118, for instance,by Z-direction movement of the pipette module 120 relative to a pipettetip 122. A pipette tip 122 can be removed from the tip adapter 118, forinstance, by movement of the pipette module 120 relative to a pipettestripper (not shown). The liquid dispenser 100 can include independentpipette tip 122 attachment or removal. The back 114 of the pipettechannel 110 is configured to reversibly connect to, or mate with, thefront 104 of the manifold 102, as described herein.

The manifold 102 in this embodiment is configured to accept as many asfive pipette channels 110. The manifold 102 can accept fewer than fivepipette channels, such as one, two, three, or four pipette channels, andis thus advantageously customizable by an operator based on theparticular liquid dispensing requirements of the operator. Although theliquid dispenser 100 shown in FIG. 1 has capacity to accept a maximum offive pipette channels 110, other configurations are contemplated. Theliquid dispenser 100 can be configured to accept a maximum of onepipette channel, two pipette channels, three pipette channels, fourpipette channels, five pipette channels, six pipette channels, sevenpipette channels, eight pipette channels, nine pipette channels, tenpipette channels, eleven pipette channels, twelve pipette channels,thirteen pipette channels, fourteen pipette channels, fifteen pipettechannels, sixteen pipette channels, seventeen pipette channels, eighteenpipette channels, nineteen pipette channels, twenty pipette channels,etc. One or more pipette channels 110 can be removed from the manifold104. In some embodiments, one pipette channel 110 can be removed withoutremoving another pipette channel 110. For instance, one pipette channel110 may be removed and replaced without removing another pipette channel110 from the manifold 102.

The mating configuration between the pipette channels 110 and themanifold 102 can have any configuration known in the art. In thenon-limiting embodiment shown in FIGS. 1B-4, the liquid dispenser 100includes one or more pegs (not visible in this view). In the illustratedembodiment, each pipette channel 110 has a peg near the top of thepipette channel 110 and a peg near the bottom of the pipette channel110. The pegs can guide alignment between the back 114 of the pipettechannel 110 and the front 104 of the manifold 102. The pegs can be dowelpins. The manifold 102 can include a corresponding slot (not shown) toaccept each of the pegs. The slots can include a chamfered edge tofacilitate insertion of the pegs. In some embodiments, the manifold 102can include at least one marking (not shown) to facilitate the alignmentof an edge of the pipette channel 110 with the manifold 102. In someembodiments, the manifold 102 has at least one edge (e.g., top edge,bottom edge, etc.) that aligns with a corresponding edge of the pipettechannel (e.g., top edge, bottom edge, etc.).

The pipette channel 110 can include one or more fasteners 124. In someembodiments, the fasteners 124 are captive screws. In the illustratedembodiment, each pipette channel 110 has a fastener 124 near the top ofthe pipette channel 110 and a fastener 124 near the bottom of thepipette channel 110. In some embodiments, the fasteners 124 can belocated near the pegs. In some embodiments, the fasteners 124 arethreaded such that the operator can securely fasten the pipette channel110 to the manifold 102. In some implementations, the fasteners 124 andpegs securing a pipette channel 110 to the manifold 102 are readilyadjustable and/or removable by an operator without affecting theoperation or connections of another pipette channel 110 that is matedwith the manifold 102. In one example, a first pipette channel 110 thatis malfunctioning, requires an adjustment, or is need of regularmaintenance or testing can be removed by an operator without affectingthe operation or connections of any other pipette channel 110 that ismated with the manifold 102. In some cases, the operator seamlesslyreplaces the first (now removed) pipette channel 110 with a secondpipette channel by connecting the second pipette channel to the manifold102 with pegs in the location previously occupied by the first (nowremoved) pipette channel 110.

The pipette channel 110 can be fixed in position to the manifold 102.The manifold 102 can be coupled to a robotic arm (not shown) which canmove the manifold 102 in space. The motion of the robotic arm can havesix degrees of freedom. For example, the robotic arm can include 1degree of translational freedom, 2 degrees of translational freedom, 3degrees of translational freedom, 1 degree of rotational freedom, 2degrees of rotational freedom, 3 degrees of rotational freedom, or anycombination of these. In some embodiments, the manifold 102 is coupledto a gantry (not shown) of an automated sample analysis system. Thegantry can include a bar or rail which allows movement of the manifold102 along an X-axis of the automated sample analysis system (“theX-direction”). The gantry can include a bar or rail which allowsmovement of the manifold 102 along a Y-axis of the automated sampleanalysis system (“the Y-direction”). Such relative motion can beaccomplished by any suitable mechanical movement device, such as but notlimited to, gearing, or a rack and pinion assembly, or a lead screw, ora belt drive, or a linear motor. In some embodiments, the manifold 102is moveable along a Z-axis of the automated sample analysis system (“theZ-direction”). In other embodiments, movement of the manifold 102 in theZ-direction is prevented.

In some embodiments, movement in the Z-direction is provided by thepipette channel 110. The module 120 can include a flange 126. The flange126 can be fixedly attached to a coupling 128. The coupling 128 ismovable along a track 130. The movement of the coupling 128 causesmovement of the module 120 in the Z-direction relative to the track 130.The track 130 is fixedly attached to a base 132 of the pipette channel110. The base 132 of the pipette channel is stationary relative tomanifold 102. The movement of the coupling 128 causes movement of themodule 120 in the Z-direction relative to the base 132 of the pipettechannel 110. The movement of the coupling 128 causes movement of themodule 120 in the Z-direction relative to the manifold 102.

FIG. 3 shows a cross-sectional view of the liquid dispenser 100 takenalong line 3-3 of FIG. 2. In some embodiments, the coupling 128 cancouple to a nut 134 which includes a bore. A plurality of ball bearingsare arranged around the bore inside the nut 134, which reduce frictionwhen interacting with the ball screw 136. In some embodiments, thecoupling 128 can be integral with the nut 134 configured to interactwith a ball screw 136. In other embodiments, the bore 134 is threadedand interacts with a lead screw (not shown). The ball screw 136 can berotated with a motor 138. The ball screw 136 can be coupled to a bearing140. The bearing 140 allows the ball screw 136 to rotate withouttranslation. As the ball screw 136 is rotated (in this embodiment, bythe motor 138), the coupling 128 translates along the ball screw 136.The coupling 128 is guided along the track 130 in the Z-direction.Rotation of the ball screw 136 in a first direction causes the coupling128 to translate downward along the track 130. Rotation of the ballscrew 136 in a second, opposite direction causes the coupling 128 totranslate upward along the track 130.

The module 120 includes a mechanism to provide aspirate and dispenseoperations. In some embodiments, a sample is only introduced into thesystem via the pipette tip 122. The movement of the coupling 128 allowsthe pipette tip 122 to be lowered into a container to aspirate and/ordispense a sample or other liquid. After aspirating or dispensing thesample or other liquid in the container, the movement of the coupling128 allows the pipette tip 122 to be raised above the a container tomove the pipette tip 122 to another location, for example over a secondcontainer in an automated sample analysis system.

The aspirate and dispense operations of the module 120 can becontrolled, in part, by application of air pressure or vacuum. Themanifold 102 can include an inlet pressure port 142. The manifold 102can include an inlet vacuum port 144. The inlet pressure port 142 can belocated on the front 104, back 106, or sides 108 of the manifold 102.The inlet vacuum port 144 can be located on the front 104, back 106, orsides 108 of the manifold 102. The inlet pressure port 142 and the inletvacuum port 144 are located on the front 104 of the manifold 102 in theembodiment of FIGS. 1B-4, but other configurations are contemplated.

The manifold 102 includes a pressure channel 146 and a vacuum channel148. The pressure channel 146 is in fluid communication with the inletpressure port 142. In some embodiments, the inlet pressure port 142provides the only entrance to the pressure channel 146. The pressurechannel 146 exits to one or more pressure cross-channels 150 describedherein. The inlet pressure 142 can, in some cases, seal the pressurechannel 146. The vacuum channel 148 is in fluid communication with theinlet vacuum port 144. In some embodiments, the inlet vacuum port 144provides the only entrance to the vacuum channel 148. The vacuum channel148 exits to one or more vacuum cross-channels 152 described herein. Theinlet vacuum port 144 can, in some cases, seal the vacuum channel 148.In some methods of manufacturing, the pressure channel 146 and/or thevacuum channel 148 are formed by drilling a bore from one side 108 ofthe manifold 102 toward the other side 108 of the manifold 102. In someembodiments, the bore is a through bore. The bore can be plugged orotherwise sealed at the sides 108 of the manifold 102. The cross-channelcan be any shape of sub-channel connecting at least in part to either apressure channel or a vacuum channel. The cross-channel can form anyangle with the pressure channel or a vacuum channel, including 30, 45degrees, 60 degrees, 75 degrees, and 90 degrees etc. The termcross-channel does not imply that the cross-channel necessarily forms a90 degree intersection with the pressure channel or a vacuum channel.

The inlet pressure port 142 can be connected to a source of pressurizedgas (not shown) via tubing (not shown). The pressurized fluid such as apressurized gas can travel from the inlet pressure port 142 through thepressure channel 146. The pressure channel 146 can supply gas underpressure to each pipette channel 110 connected to the manifold 102.

Similarly, the inlet vacuum port 144 can be connected to a vacuum source(not shown) via tubing (not shown). Gas in the vacuum channel 148 can besupplied with gas under vacuum via the inlet vacuum port 144 and thevacuum source. The vacuum channel 148 can supply gas under vacuum toeach pipette channel 110 connected to the manifold 102. The pressurechannel 146 and the vacuum channel 148 can be parallel bores through themanifold 102, as shown. The inlet pressure port 142 and the inlet vacuumport 144 can have standard connectors, for example industry-standardconnectors that mate with suitable pneumatic tubing.

Referring to FIG. 4, the pressure channel 146 is shown extending throughthe manifold 102. The pressure channel 146 is connected to a pressurecross-channel 150. The pressure cross-channel 150 extends from thepressure channel 146 in the manifold 102 to the base 132 of the pipettechannel 110. The pressure cross-channel 150 extends from the front ofthe manifold 102 to the back of the pipette channel 110. The pressurecross-channel 150 can be perpendicular to the pressure channel 146.

Similarly, the vacuum channel 148 is shown extending through themanifold 102. The vacuum channel 148 is connected to a vacuumcross-channel 152. The vacuum cross-channel 152 extends from the vacuumchannel 148 in the manifold 102 to the base 132 of the pipette channel110. The vacuum cross-channel 152 extends from the front of the manifold102 to the back of the pipette channel 110. The vacuum cross-channel 152can be perpendicular to the vacuum channel 148. In some embodiments, onepipette channel 110 can be removed from the liquid dispenser 100 (forexample, disconnected from the front 104 of the manifold 102). Thecorresponding now-exposed pressure cross-channel 150 and vacuumcross-channel 152 may need to be covered. For instance, if one pipettechannel 110 is removed, the user may install a blanking plate (notshown) that covers the exposed pressure cross-channel 150 and vacuumcross-channel 152. The blanking plate can include a peg near the top ofthe blanking plate and a peg near the bottom of the blanking plate. Theblanking plate can include a fastener 124 near the top of the blankingplate and a fastener 124 near the bottom of the blanking plate. Othermechanisms configured to cover one or more of the pressure cross-channel150 and vacuum cross-channel 152 are contemplated includes seals, plugs,adhesives, etc. The pressure cross-channel 150 and vacuum cross-channel152 can be sealed such that one or more pipette channels 110 can beremoved without adversely impacting the aspirate and dispense operationsof another pipette channel 110 mated with the manifold 102.

As described herein, the pipette channel 110 is modular allowing thepipette channel 110 to be reversibly secured to and disconnected fromthe manifold 102. The pressure cross-channel 150 and the vacuumcross-channel 152 are structures in the manifold 102. The pressurecross-channel 150 associated with each pipette channel 110 spans adistance between the pressure channel 146 and a pressure port 156 on theback 114 of the pipette channel 110 when the pipette channel 110 issecured to the front 104 of the manifold 102. The vacuum cross-channel152 associated with each pipette channel 110 spans a distance betweenthe vacuum channel 148 and a vacuum port 157 on the back 114 of thepipette channel 110 when the pipette channel 110 is secured to the front104 of the manifold 102. In some embodiments, the liquid dispenser 100includes one or more features to improve the seal between the pipettechannel 110 and the manifold 102. In some embodiments, an o-ring 154seals a fluidic connection (for transfer of a gas, for example) betweenthe pipette channel 110 and the manifold 102. The o-rings 154 can belocated near the pressure cross-channel 150 and the vacuum cross-channel152.

Embodiments of pressure channels 110 of described herein include anindividually-actuatable solenoid valve 158 configured to control theflow of gas from the manifold 102 to the module 120 of the pressurechannel 110. One pressure cross-channel 150 and one vacuum cross-channel152 of the manifold 102 are each connected to the solenoid valve 158 ofa corresponding pipette channel 110 when the pipette channel is mated tothe manifold 102. The solenoid valve 158 can be located within the base132 of the pipette channel 110. The solenoid valve 158 acts as aselector between vacuum and pressure.

In a first position, the solenoid valve 158 directs pressurized fluid,such as a gas under pressure, from the pressure cross-channel 150through a tube 160. The tube 160 extends from the solenoid valve 158 tothe module 120. In this first position of the solenoid valve 158, thetube 160 supplies pressurized fluid to the module 120. In someembodiments, pressurized fluid can act on a piston within the module 120to dispense fluid from the pipette tip 122. In some embodiments, themodule 120 can include a second valve (not shown) configured to controlthe aspirate or dispense operations. The second valve can be a solenoidvalve. The second valve uses pressure and/or vacuum to control theaspirate or dispense operations. The module 120 can include a flowsensor to determine how much was aspirated or dispensed.

In a second position, the solenoid valve 158 directs fluid under vacuum,such as a gas under vacuum, from the vacuum cross-channel 152 throughthe tube 160. In other embodiments, the gas under vacuum is directedthrough a second tube 162. The tube 162 extends from the solenoid valve158 to the module 120. In this second position of the solenoid valve158, the tube 160 (or the tube 162, depending on the implementation)supplies gas under vacuum to the module 120. For instance, gas undervacuum can be supplied to the second valve within the module 120 toaspirate fluid into the pipette tip 122.

The solenoid valve 158 is integrated within the base 132 of the pipettechannel 110. Advantageously, if a solenoid valve in a single pipettechannel 110 of the liquid dispenser 100 malfunctions, requiresmaintenance, testing, inspection, or any other process requiring accessto the solenoid valve 158, the entire pipette channel 110 with theaffected solenoid valve 158 can be removed from the liquid dispenser 100and replaced with another pipette channel 110. The pipette channel 110forms a seal with the manifold 102 such that pressure and/or vacuum canbe transferred from the manifold 102 to the pipette channel 110. Whenthe pegs are aligned with the manifold during installation of thepipette channel 110, the pressure cross-channel 150 and the vacuumcross-channel 152 create a continuous pathway for gas under pressure andgas under vacuum. The pipette channel 110 and the manifold 102 form apneumatic connection via the pressure cross-channel 150 and the vacuumcross-channel 152. The pneumatic connection can be a physical connectionwhich is formed when the pipette channel 110 mates with the manifold102.

The manifold 102 can be a pneumatic manifold to supply fluid undervacuum and pressurized fluid to each pipette channel 110. In someembodiments, the pneumatic solenoid valve 158 is integrated into eachpipette channel 110 and acts as a selector between vacuum and pressure.Pneumatic tubing is reduced or eliminated by integrated, modularpathways in the manifold 102 and the pipette channels 110 of the presentdisclosure. The integrated pathways can be sealed with o-rings at theinterface between the manifold 102 and the pipette channels 110. Tubingbetween the solenoid valve 158 and the pipette channel 110 can beeliminated by placement of the solenoid valve 158 within the base 132 ofthe pipette channel 110.

The pipette channel 110 can form an electrical connection with themanifold 102. The electrical connection can include a physicalconnection which is formed when the pipette channel 110 mates with themanifold 102. As shown in FIG. 3, the pipette channel 110 can include anelectrical connector 166 on the back side 114 of the pipette channel110. The electrical connector 166 can be coupled to a circuit board 168within the pipette channel 110. Each pipette channel 110 can include acircuit board 168 and corresponding electrical connector 166. Themanifold 102 can include one or more electrical connectors 170 on thefront side 104 of the manifold 102. Each electrical connector 170 isconfigured to electrically connect to a corresponding circuit board 168of a pipette channel 110 mated with the manifold 102. The electricalconnector 170 can be considered a backplane connector. The manifold 102can include a circuit board 172. The electrical connectors 166, 170 canallow communication of electrical signals and control signals betweenthe manifold 102 and the pipette channel 110. As described herein, thecontrol signals can be data signals designed to control one or moreoperations of the pipette channel 110. The electrical signals caninclude electrical power to the components of the pipette channel 100,such as AC/DC electricity. The electrical connectors 166, 170 can allowcommunication of electrical signals between the circuit boards 168, 172.The circuit boards 168, 172 can be printed circuit boards. The matingelectrical connectors 166, 170 can eliminate or reduce electrical cablesand/or connections that are required to form an electrical connectionbetween the manifold 102 and the pipette channels 110. The module 120can include circuit board 164. The circuit board 164 can be associatedwith the aspirate and dispense operations. The circuit boards 164, 168,and/or 172 can be electrically connected. In some embodiments, circuitboards 164 and 168 are physically connected via a ribbon cable 176. Theribbon cable 176 can extend along the coupling 128 at the interfacebetween the pipette channel 110 and the module 120. The ribbon cable 176can transmit control signals and electrical signals. In someembodiments, movement in the Z-direction of the pipette tip 122 engagedto the module 120 is controlled by features housed in the pipettechannel 110, for instance, controlled by the circuit board 168. Thez-axis control hardware can be located within the pipette channel, forinstance on circuit board 168. In some embodiments, the circuit board164 acts as an interconnect board and also contains the capacitive sensecircuit.

The manifold 102 can include one or more additional electricalconnectors 174. In FIGS. 1B-4, the manifold includes three electricalconnectors 174. The electrical connectors 174 can include differentconfigurations and shapes to accommodate different electricalconnections. The electrical connectors 174 can include an Ethernetconnection. The Ethernet connection can provide signals to the circuitboards 168, 172. The electrical connectors 174 can include a powerconnector. The power connector can supply electrical power to the motor138 and the solenoid valve 158 within each of the pipette channels 110when they are mated to the manifold 102. The electrical connector 174can include a module connection. The module connection can control themodule 120, for instance the aspirate and dispense operations of themodule 120. Other electrical connectors 174 are contemplated. One ormore electrical connectors 174 can be located on the front 104, back106, or sides 108 of the manifold 102. In the illustrated embodiments,all of the electrical connectors 174 are located on the front 104 of themanifold 102. In some embodiments, the number of electrical connectors174 does not depend on the number of pipette channels 110. For instance,in the illustrated embodiment, three electrical connectors 174 areincluded regardless of the maximum number of pipette channels 110 themanifold 102 can accept.

The pipette channel 110 can be designed to accommodate internal wiringand tubing. The pipette channel 110 can house the tubes 160, 162extending from the solenoid valve 158 to the module 120. The pipettechannel 110 can include a ribbon cable 176 which transmits electricalsignals and control signals. The electric signals can include signalsfrom the electrical connectors 174. The ribbon cable 176 can extend fromthe electrical connector 166 on the back side 114 of the pipette channelto the module 120. The tube 160, the tube 162 (if included), and theribbon cable 176 can each include a bend 178. The bends 178 in the tube160, 162 and the ribbon cable 176 are shown in an upward position inFIG. 4. The upward position of the bends 178 in the tubes 160, 162 andthe ribbon cable 176 corresponds to an upward position of the module120. As the module 120 moves downward, the bends 178 in the tubes 160,162 and in the ribbon cable 176 move downward within the base 132 of thepipette channel 110. The bends 178 in the tubes 160, 162 and in theribbon cable 176 can be accommodated within a groove 180 in the base 132of the pipette channel 110.

In the illustrated embodiment, the five pipette channels 110 are locatedto the left of the electrical connectors 174, the inlet pressure port142, and the inlet vacuum port 144. Implementations of manifold 102described herein can be configured to accept additional pipette channels110, which may increase the width of the manifold in the X-direction.Decreasing the number of pipette channels 110 the manifold 102 isconfigured to accept may decrease the width of the manifold 102 in theX-direction. The pipette channels 110 can be arranged such that thepipette tips 122 are aligned. The distance between adjacent pipette tips122 can be designed to accommodate the spacing of the associatedcontainers for the aspirate and dispense operation. In the illustratedembodiments, the pipette tips 122 are 18 mm apart center to center. Theassociated containers are 9 mm apart center to center. Accordingly, inthis non-limiting arrangement, the pipette tips 122 can engage everyother container (e.g., a first subset of the containers) in a firstposition. The liquid dispenser 100 can be moved 9 mm to the right orleft in the X-direction to engage every other container (e.g., a secondsubset of the containers).

In an embodiment not shown, features of manifold 102 can be incorporatedwithin a plurality of pipette channels 110 that are permanently securedin a stacked formation adjacent to each other, thereby eliminating themanifold 102. The electrical connector 166 of each pipette channel 110can be located on a side 116 of the pipette channel 110 to communicatesignals to and from adjacent pipette channels 110. The pressure channel146 can extend through the stacked pipette channels 110. The vacuumchannel 148 can extend through the stacked pipette channels 110. One ormore o-rings 154 can seal the pressure channel 146 and/or vacuum channel148 between the stacked pipette channels 110. The pressure channel 146and vacuum channel 148 can connect to pressure cross-channels 150 andvacuum cross-channels 152 as described herein.

Embodiments described herein advantageously enable independent movementof each of a plurality of modules 120 along the Z-axis direction,allowing each of a plurality of samples to be independently andsimultaneously aspirated and dispensed within the liquid dispenser 100.In configurations that include more than one pipette channel, each ofthe plurality of pipette channels includes an individually-actuatablecoupling 128 that moves along a ball screw 136 to translate the module120 (independently of other modules 120) relative to the base 132 of thepipette channel 110.

Embodiments described herein also advantageously reduce pneumatic tubingto modular, individually-actuatable pipette channels. Independentlyoperating multiple pipette channels 110 positioned next to each otherwould typically require multiple pneumatic tubes running to each pipettechannel 110 from a common pneumatic pressure and vacuum source. Thecommon pneumatic pressure and vacuum source can be a remotely mountedsolenoid valve manifold. The remotely mounted solenoid valve manifoldmakes it difficult to route the tubing to each pipette channel 110. Insuch an arrangement, the pneumatic tubes running to each pipette channel110 would be both visible and cumbersome. The multiple pneumatic tubesmay impede motion, such as motion of the liquid dispenser along agantry. The remotely mounted solenoid valve manifold would require muchlonger tubing or multiple sections of tubing to span from the remotelymounted solenoid valve manifold to each pipette channel 110. Incontrast, liquid dispensers described herein reduce pneumatic tubingdown to two pneumatic tubes connecting to the manifold 102; that is, onepneumatic tube (not shown) connecting to the inlet pressure port 142 andone pneumatic tube (not shown) connecting to the inlet vacuum port 144.Each pipette channel 110 is supplied pressurized gas and gas undervacuum through the pressure channel 146 and vacuum channel 148,respectively. This eliminates separate pneumatic tubing to each pipettechannel 110. In other embodiments, separate pneumatic tubing is suppliedto each pipette channel 110. In some embodiments, a separate piece ofpneumatic tubing 160, 162 is provided inside each pipette channel 110that connects the module 120 to the solenoid valve 158. Such embodimentsare still advantageous over systems using a remotely mounted solenoidmanifolds because the tubing 160, 162 is very short and self-containedinside the pipette channel 110 and module 120.

Advantageously, embodiments described herein also reduce electricalconnections to modular, individually-actuatable pipette channels.Independently operating multiple pipette channels 110 positioned next toeach other would typically require multiple electrical cables running toeach pipette channel 110 from a common controller. The embodimentsdescribed herein reduce electrical cables down to three electricalconnectors 174 connecting to the manifold 102. Each pipette channel 110is electrically connected to the electrical connectors 174. Forinstance, signals from the Ethernet connection are sent to each pipettechannel 110 that is interchangeably mated to the manifold 102. Foranother example, signals from the module connection are sent to eachmodule 120 of the plurality of pipette channels 110 that areinterchangeably mated to the manifold 102. This eliminates separatecabling to each pipette channel 110. In other embodiments, separateelectrical connections are provided to each pipette channel 110.

Embodiments described herein also eliminate pneumatic tubing between thesolenoid valve 158 and the pipette channel 110. Typically, a separatepneumatic solenoid manifold would be mounted in close proximity to thepipette channels 110. Pneumatic tubing would connect the solenoidmanifold to each pipette channel 110. In contrast, in some embodimentsof the present disclosure, the solenoid valve 128 is integrated withinthe pipette channel 110. Each pipette channel 110 can include a solenoidvalve 158. This eliminates the separate solenoid manifold and theassociated pneumatic tubing running from the separate solenoid manifoldto each pipette channel 110. In other embodiments of the presentdisclosure, the solenoid valves 158 are not located within the pipettechannels 110. The solenoid valves can be located in the manifold 102.Pneumatic cross-channels similar to those described above can connectthe solenoid valves in the manifold 102 to channels in the pipettechannels 110 mated to the manifold 102. In these alternativeembodiments, pneumatic tubing is still eliminated because pneumaticcross-channels between the manifold 102 and the modular,individually-actuatable pipette channels 110 are formed when the pipettechannels 110 are mated to the manifold 102.

One advantage of some embodiments described herein includes independentoperation of each pipette channel 110. In some embodiments, each pipettechannel 110 can independently control the Z-movement of the pipettemodule 120. In some embodiments, each pipette channel 110 canindependently control the aspirate and/or dispense operations of thepipette module 120. In some embodiments, each pipette module 120 iscontrolled independently. In some embodiments, two or more pipettemodules 120 can move simultaneously, in the same or differentoperations. In some embodiments, each pipette channel 110 includes oneor more solenoid valves 158 which selects between vacuum and pressure.In some embodiments, the second valve within the module 120independently controls aspirate and dispense operations.

Another advantage of some embodiments described herein includes smalleroverall package size. The modular pipette channels 110, 210, 310, 410described herein can be compact. In one non-limiting example, a singlepipette channel 110, 210, 310, 410 in accordance with the presentdisclosure is 0.689 inches (or 17.5 mm) wide in the X-direction, 7.020inches (or 178.3 mm) deep in the Y-direction, and 13.228 inches (or 336mm) tall in the Z-direction. Implementations of the manifold 102, 202,302, 402 described herein can be compact. In one non-limiting example,the manifold 202 in accordance with the present disclosure is 3.8583inches (or 98 mm) wide in the X-direction, 2.0472 inches (or 52 mm) deepin the Y-direction, and 15.1969 inches (or 386 mm) tall in theZ-direction. In one non-limiting example, the manifold 402 in accordancewith the present disclosure is 3.295 inches (or 83.7 mm) wide in theX-direction, 0.8268 inches (or 21 mm) deep in the Y-direction, and13.2283 inches (or 336 min) tall in the Z-direction. The module 120,220, 320, 420 can be compact. In one non-limiting example, a module 120,220, 320, 420 in accordance with the present disclosure is 0.6693 inches(or 17 mm) wide in the X-direction, 3.0551 inches (or 77.6 mm) deep inthe Y-direction, and 10.2441 inches (or 260.2 mm) tall in theZ-direction including the tip adaptor 118, 218, 318, 418. As a result ofthe compact nature of pipette channels, manifolds, and modules describedherein, the lengths of tubing and/or wiring can be reduced. In someembodiments, faster switching between vacuum and pressure can beaccomplished due to the close proximity of the solenoid valve 158 to themodule 120.

Still another advantage of embodiments described herein includes themodularity of the pipette channels 110. One or more pipette channels 110can be removed and/or replaced without removing one or more adjacentpipette channels 110. In some embodiments, there is an ability toquickly swap out individual pipette channels 110.

Advantages described above with reference to the liquid dispenser 100illustrated in FIGS. 1B-4 are also applicable to other liquid dispensersof the present disclosure, for example liquid dispenser 1, liquiddispenser 200, liquid dispenser 300, liquid dispenser 400, and liquiddispenser 500 described in detail below.

FIGS. 5-34 show views of a liquid dispenser 200 according to anotherembodiment of the present disclosure. The liquid dispenser 200 caninclude features that are substantially similar to features describedabove with reference to the liquid dispenser 100. For example, theliquid dispenser 200 can include the features of a manifold 202, with afront 204, a back 206, and sides 208. The liquid dispenser 200 caninclude the features of one or more pipette channels 210, with a front212, back 214, and sides 216. The liquid dispenser 200 can include thefeatures of a module 220 with a flange 226, a coupling 228, a pipettetip 222, and a tip adapter 218. The liquid dispenser 200 can include thefeatures of a track 230 and a base 232. The liquid dispenser 200 caninclude the features of a nut 234 configured to interact with a ballscrew 236, a motor 238, and a bearing 240. The liquid dispenser 200 caninclude the features of an inlet pressure port 242, an inlet vacuum port244, a pressure channel 246, a vacuum channel 248, a pressurecross-channel 250, a vacuum cross-channel 252, a pressure port 256, avacuum port 257, and one or more o-rings 254. The liquid dispenser 200can include the features of a solenoid valve 258, and one or more tubes260, 262. The liquid dispenser 200 can include the features of aconnector 266 and circuit board 268 of the of the pipette channel 210.The liquid dispenser 200 can include the features of a connector 270 andcircuit board 272 of the manifold 202. The liquid dispenser 200 caninclude the features of a circuit board 264 of the module 220. Theliquid dispenser 200 can include the features of electrical connectors274. The liquid dispenser 200 can include the features of a ribbon cable276, a bend 278, and a groove 280. The liquid dispenser 200 can includeany of the features of the liquid dispensers described herein.

In this non-limiting embodiment, the inlet pressure port 242 and theinlet vacuum port 244 of the liquid dispenser 200 are located on theback 206 of the manifold 202. The electrical connectors 274 are alsolocated on the back 206 of the manifold 202. Embodiments of liquiddispensers described herein that employ this configurationadvantageously reduce the width of the liquid dispenser 200 along theX-direction. The circuit board 264 of the module 220 can be shorter inthe Z-direction than the embodiment in FIGS. 1B-4. The circuit board 264and the module 220 can be enclosed in a housing.

The liquid dispenser 200 can include a-mechanism configured to eject asingle pipette tip of a plurality of pipette tips 222, as shown in FIGS.30-31. The liquid dispenser can include a tip eject motor 282. The tipeject motor 282 can be connected to a translating sleeve 284 thatencases a portion of the tip adapter 218. The tip eject motor 282 canrotate which exerts a downward force on the sleeve 284, causing it tomove in the Z-direction relative to the tip adapter 218. The downwardforce on the sleeve 284 overcomes a friction fit between the pipette tip222 and the tip adapter 218 such that the pipette tip 222 is ejected ordisengaged from the tip adapter 218.

The liquid dispenser 200 can include features which sense whether apipette tip 222 is engaged with the module 220. The liquid dispenser 200can include a sensor 286. In some embodiments, the sensor 290 is a REEDsensor which senses a magnetic field. A component associated with thepipette tip 222 such as the sleeve 284 can include a magnet 286. Apipette tip 222 is engaged when the motor 238 drives the entire module220 down to engage the pipette tip 222. The motor 238 in thisimplementation is the main z-axis motor. When the module 220 engages thepipette tip 222, the sleeve 284 translates upward from contact with thepipette tip 222 to allow the pipette tip 222 to engage the tip adapter218. To engage a pipette tip 222, the module 220 translates downward inthe Z-direction and pushes down on the pipette tip 222 until the pipettetip 222 snaps on, forms a friction fit, or otherwise engages the tipadapter 218. When a pipette tip 222 is loaded on the module 220 and thesleeve 284 is in this first, “engaged” position, the magnet 286 is inclose proximity to the sensor 290. The pipette tip 222 can be ejected asdescribed herein. The pipette tip 222 can become inadvertentlydisengaged during operation of the liquid dispenser 200. In suchinstances, the sleeve 284 and the magnet 286 fall downward in theZ-direction under the influence of gravity, causing the magnet 286 to belocated further away from the sensor 290 than when the sleeve 284 was inthe first “engaged” position before the pipette tip 222 becamedisengaged. The sensor 290 can indicate whether a pipette tip 222 isengaged with the sleeve 284 based on the distance between the sensor 290and the magnet 286. The sensor 290 can determine whether a pipette tip222 is present on the tip adapter 218.

The liquid dispenser 200 can include features which provide capacitivesense. Capacitive sensing is performed by an electrical circuit that islocated on the small board (not shown) on the module 220. The board isconnected via a wire, cable, or flex circuit to the tip adapter 218.When the tip adapter 218 makes contact with a liquid or other object,the circuit sees a change. The tip adapter 218 can be electricallyisolated from the rest of the module 220, except for the wire going tothe circuit board. The liquid dispenser 200 can include other featureswhich determine liquid levels such as liquid levels in the pipette tip.The capacitive sense circuit can determine the Z-direction height ordistance of the module 220 relative to a container containing a sampleto be dispensed or aspirated. The liquid dispenser 200 can be configuredto sense or receive a signal indicating, and in some cases store,information on the Z-direction height, for instance the height toassociated containers. The liquid dispenser 200 can be configured tosense or receive signals indicating, and in some cases, storeinformation on multiple heights associated with different containers.The liquid dispenser 200 can return to a stored height during aspirateand dispense operations. Other embodiments of liquid dispensersdescribed herein, such as but not limited to liquid dispenser 100,liquid dispenser 300, liquid dispenser 400, and liquid dispenser 500,can also include capacitive sense features.

The liquid dispenser 200 can include features which provide magneticbraking such as a hysteresis brake, as shown in FIGS. 34A and 34B. Theball screw 236 can include or be coupled to a disc 294. The ball screw236 can include a coupling portion 237. In FIG. 34A, the couplingportion 237 is threaded. The coupling portion 237 can be inserted into athreaded bore of the disc 294. The coupling portion 237 can be insertedinto a threaded bore of a bearing 239. The bearing 239 can facilitatealignment between the ball screw 236 and the disc 296. In FIG. 34B, thecoupling portion 237 includes one or more grooves. In some embodiments,the disc 294 includes one or more projections designed to engage thegrooves. In some embodiments, the disc 294 includes a mechanism designedto couple the coupling portion 237 with the disc 294. Otherconfigurations of coupling the ball screw 236 and the disc 294 arecontemplated. In some embodiments, the ball screw 236 and the disc 294are rotational coupled such that rotation of the ball screw 236 causesrotation of the disc 294.

The bearing 239 or other portion of the pipette channel 210 can includea disc 296. The disc 296 can include one or more magnets 298. In someembodiments, a plurality of magnets 298 in the disc 296 can all have thesame polarity. In some embodiments, the magnets 298 in the disc 296 havethe opposite polarity. In some embodiments, the magnets 298 in the disc296 have alternating polarity. In some embodiments, adjacent magnets 298can have opposite polarity. The disc 294 can be a hysteresis disc. Insome embodiments, only the disc 296 includes magnets 298. Duringrotation of the ball screw 236 under the influence of the motor 238, themotor 238 overcomes a magnetic force created by the magnetic interactionof the discs 294, 296. When the motor 238 stops, the magnets 298 in thedisc 296 are attracted to disc 294. The magnetic force is sufficient toapply a torque to the ball screw 236 to reduce and/or prevent rotationof the ball screw 236. The magnetic force can be sufficient to reduceand/or prevent the free-fall of the coupling 228 along the track 230 inthe event of loss of electrical power to the pipette channel 210. Otherembodiments of liquid dispensers described herein, such as but notlimited to liquid dispenser 100, liquid dispenser 300, liquid dispenser400, and liquid dispenser 500, can also include magnetic brakingfeatures. FIG. 34B shows a modified design in which the disc 296 can becoupled to or integrally formed with a block 299. The block 299 cananchor the disc 296 to the pipette channel 210. The block 299 caninclude an attachment section for coupling with pegs or fasteners. Theattachment section can include one or more curved corners. The block 299can be polygonal or generally polygonal. In the illustrated embodiment,the block 299 is diamond shaped with rounded corners.

FIGS. 34C and 34D show other features of the liquid dispenser. The ballscrew 236 can be rotated with a motor 238. The coupling 228 can includea nut which includes a bore 229. In some embodiments, a plurality ofball bearings (not shown) are arranged around the bore 229 inside thenut, which reduce friction when interacting with the ball screw. Theball bearing s can rotate within a helical groove of the ball screw 236.As one example, as the ball screw 236 rotates, a ball bearing travelsaround the ball screw 236 within the groove of the ball screw 236 and agroove in the nut. When the ball bearing reaches the top of the nut, theball bearing is fed down a channel in the coupling 228 (not shown)toward the bottom of the nut. The ball screw 236 can be rotated in theopposite direction such that the ball bearing is fed up the channel inthe coupling 228. FIGS. 34C and 34D show how the coupling 228 isattached to the ball screw 236. FIGS. 34C and 34D also show how themotor 238 and the ball screw 236 are coupled. In some embodiments, thepipette channel 210 can include an integrated ball screw assembly whichcan include one or more of the motor 238, an encoder, and the ball screw236. In some embodiments, the motor 238 and the encoder are coupled asan assembly or integrally formed.

FIG. 34C shows a shaft coupling 241. The shaft coupling 241 couples theshaft of the ball screw 236 and the shaft of the motor 238. The shaftcoupling 241 can allow for a degree of misalignment between the ballscrew 236 and the motor 238. The shaft coupling 241 accounts formisalignment between the ball screw 236 and the shaft of the motor 238.The shaft coupling 241 can tolerate some angular misalignment. The shaftcoupling 241 can be designed to handle axial misalignment between theball screw 236 and the motor 238. In some embodiments, the shaftcoupling 241 can allow a misalignment of 1 degree, 2 degrees, 3 degrees,4 degrees, 5 degrees, 6 degrees, 7 degrees, 8 degrees, 9 degrees, 10degrees, 11 degrees, 12 degrees, 13 degrees, 14 degrees, 15 degrees,between 0-5 degrees, between 0-10 degrees, etc.

The liquid dispenser 200 can include one or more bearings 245. Thebearings 245 can support the end of the ball screw 236. The bearings 245can include a matched set of angular contact bearings. The bearings 245can support the ball screw 236 in both the radial and axial directions.In some embodiments, the bearing 245 allows the ball screw to rotatewithout translation. In some embodiments, the bearing 245 reduces axialmisalignment between the motor 238 and the ball screw 236.

As described herein, the coupling 228 can include a portion thatinteracts with the ball screw 236 and a portion that interacts with thetrack 230. FIG. 34D shows an embodiment of these two portions. In someembodiments, the coupling 228 can be a floating coupling that allows theconnection between the track 230 and the ball screw 236 to self-adjustor float. The floating coupling provides flexibility to prevent bindingif the track 230 and the ball screw 236 are not perfectly aligned. Insome embodiments, a bearing supports the ball screw axially andradially. In some embodiments, one or more bearings are integrated withthe motor 238. In other embodiments, one or more bearings are separatecomponents from the motor 238.

Embodiments of the magnetic brake described herein advantageously limitundesirable movement of the pipette tip. Another advantage is that themagnetic brake limits damage to the pipette tip. In addition,embodiments of the magnetic brake described herein advantageouslyprovide greater drive accuracy. Still another advantage is that themagnetic brake allows controlled movement of the pipette tip relative toa container. In some embodiments, the magnetic brake functions to limitmovement of the pipette tip. In some embodiments, the force produced bythe magnetic brake limits downward or upward movement of the module 220when the motor 238 stops.

FIGS. 35-55 show views of a liquid dispenser 300 according to anotherembodiment of the present disclosure. The liquid dispenser 300 caninclude features that are substantially similar to features describedabove with reference to the liquid dispenser 100 and the liquiddispenser 200. For example, the liquid dispenser 300 can include thefeatures of a manifold 302, with a front 304, a back 306, and sides 308.The liquid dispenser 300 can include the features of one or more pipettechannels 310, with a front 312, back 314, and sides 316. The liquiddispenser 300 can include the features of a module 320 with a flange326, a coupling 328, a pipette tip (not, shown but similar to pipettetips 122, 222), and a tip adapter 318. The liquid dispenser 300 caninclude the features of a track 330 and a base 332. The liquid dispenser300 can include the features of a nut 334 configured to interact with aball screw 336, a motor 338, and a bearing 340. The liquid dispenser 300can include the features of an inlet pressure port 342, an inlet vacuumport 344, a pressure channel 346, a vacuum channel 348, a pressurecross-channel 350, a vacuum cross-channel 352, a pressure port 356, avacuum port 357, and one or more o-rings 354. The liquid dispenser 300can include the features of a solenoid valve 358, and one or more tubes360, 362. The liquid dispenser 300 can include the features of aconnector 366 and circuit board 368 of the of the pipette channel 310.The liquid dispenser 300 can include the features of a connector 370 andcircuit board 372 of the manifold 302. The liquid dispenser 300 caninclude the features of a circuit board 364 of the module 320. Theliquid dispenser 300 can include the features of electrical connectors374. The liquid dispenser 300 can include the features of a ribbon cable376, a bend 378, and a groove 380. The liquid dispenser 300 can includefeatures that eject the pipette tip including a tip eject motor 382 anda sleeve 384. The liquid dispenser 300 can include any of the featuresof the liquid dispensers described herein.

In this non-limiting embodiment, the pipette module 320 is mountedadjacent to a side 316 of the pipette channel 310 along the X-axis ofthe liquid dispenser 300. Embodiments of liquid dispensers describedherein that employ this configuration advantageously decrease the depthof the pipette channel 310 along the Y-axis. Embodiments of liquiddispensers described herein that employ this configuration can increasethe width of the pipette channel 310 along the X-axis. The back 314 ofthe pipette channel 310 is configured to mate with the front 304 of themanifold 302, as described herein.

FIG. 39 shows an exploded view of the manifold 302. The aspirate anddispense operations of the module 320 can be controlled, in part, byapplication of gas pressure or gas under vacuum. The manifold 302 caninclude the inlet pressure port 342. The manifold 302 can include theinlet vacuum port 344. The inlet pressure port 342 can be located on thefront 312 of the manifold 302. The inlet vacuum port 344 can be locatedon the front 312 of the manifold 302. The inlet pressure port 342 andthe inlet vacuum port 344 can be enclosed in a housing as shown. Theelectrical connectors 374 can be located on the front 312 of themanifold 302. The electrical connectors 374 can also be enclosed in ahousing as shown.

The pressure channel 346 and the vacuum channel 348 within the manifold302 can be non-linear, for instance, having one or more bends or curvesalong the length of the channel, such as but not limited to an L-shapedor U-shaped channel. The pressure cross-channel 350 and the vacuumcross-channel 352 within the manifold 302 can be non-linear. Thepressure channel 346 and the vacuum channel 348 can extend from theinlet pressure port 342 and inlet vacuum port 344 to the pressurecross-channel 350 and the vacuum cross-channel 352, respectively. Thepressure channel 346, the vacuum channel 348, the pressure cross-channel350 and the vacuum cross-channel 352 can be designed in any way in orderto align with the pressure port 356 and the vacuum port 357 of thepipette channel 310.

The manifold 302 is configured to accept one or more pipette channels310. The liquid dispenser 300 in the illustrated embodiment isconfigured to accept one pipette channel 310, but other configurationsare contemplated. The pipette channel 310 can be fixed in position tothe manifold 302 during operation of the pipette module 320, forinstance by the pegs 324. The inlet pressure port 342 can supply gasunder pressure to one pressure cross-channel 350. The inlet vacuum port344 can supply gas under vacuum to one vacuum cross-channel 352.

The pipette module 320 is mounted adjacent to a side 316 of the pipettechannel 310. The flange 326 and the coupling 328 can be shaped toaccommodate this configuration. In some embodiments, the flange 326and/or the coupling 328 are perpendicular to the module 320. The flange326 can be fixedly attached to a coupling 328. The coupling 328 ismovable along a track 330. The movement of the coupling 328 causesmovement of the module 320 in the Z-direction relative to the track 330.The track 330 is fixedly attached to a base 332 of the pipette channel310. The base 332 of the pipette channel is stationary relative tomanifold 302. The movement of the coupling 328 causes movement of themodule 320 in the Z-direction relative to the base 332 of the pipettechannel 310 and the manifold 302. The coupling 328 can interact with aball screw 336, as described herein with reference to other embodimentsof the present disclosure.

FIGS. 56-57 show views of a liquid dispenser 400 according to anotherembodiment of the present disclosure. The liquid dispenser 400 caninclude features that are substantially similar to features describedabove with reference to the liquid dispenser 100, the liquid dispenser200, and the liquid dispenser 300. For example, the liquid dispenser 400can include the features of a manifold 402, with a front 404, a back406, and sides 408. The liquid dispenser 400 can include the features ofone or more pipette channels 410, with a front 412, back 414, and sides416. The liquid dispenser 400 can include the features of a module 420with a flange 426, a coupling 428, a pipette tip 422, and a tip adapter418. The liquid dispenser 400 can include the features of a track 430and a base 432. The liquid dispenser 400 can include the features of anut configured to interact with a ball screw, a motor 438, and abearing. The liquid dispenser 400 can include the features of an inletpressure port, an inlet vacuum port, a pressure channel, a vacuumchannel, a pressure cross-channel, a vacuum cross-channel, a pressureport, a vacuum port, and one or more o-rings. The liquid dispenser 400can include the features of a solenoid valve, and one or more tubes. Theliquid dispenser 400 can include the features of a connector and circuitboard of the of the pipette channel 410. The liquid dispenser 400 caninclude the features of a connector and circuit board of the manifold402. The liquid dispenser 400 can include the features of a circuitboard of the module 420. The liquid dispenser 400 can include thefeatures of electrical connectors. The liquid dispenser 400 can includethe features of a ribbon cable, a bend, and a groove. The liquiddispenser 400 can include any of the features of the liquid dispensersdescribed herein.

Although certain features are not shown in FIGS. 56-57, exampleimplementations of these features are described above with reference toliquid dispensers 1, 100, 200, and 300. For example, the nut, the ballscrew, the bearing, the inlet pressure port, the inlet vacuum port, thepressure channel, the vacuum channel, the pressure cross-channel, thevacuum cross-channel, the pressure port, the vacuum port, the one ormore o-rings, the solenoid valve, one or more tubes, the connector ofthe manifold, the circuit board of the manifold, the circuit board ofthe module, the electrical connectors, the ribbon cable, the bend, andthe groove are not shown in FIGS. 56-57, but it will be understood thatexample implementations of these features are described above withreference to liquid dispensers 1, 100, 200, and 300 and are applicableto the liquid dispenser 400.

In some embodiments, the liquid dispenser 400 can include pipettechannels 410 similar to pipette channels 210. In some embodiments, theliquid dispenser 400 can include manifold 402 similar to manifold 302.The manifold 402 is configured to accept one or more pipette channels410. The inlet pressure port 442 can supply gas under pressure to one ormore pressure cross-channels. The inlet vacuum port 444 can supply gasunder vacuum to one or more vacuum cross-channels.

Example Liquid Dispensers According to the Present Disclosure

FIGS. 58-60 show views of the liquid dispenser 200 described aboveoperably coupled to a robot 500. The robot 500 in this implementation isa separate robotic assembly that is used to perform various functionswithin a diagnostic testing system, for example pick up PCR plates inthis example diagnostic testing system. The robot 500 travels with theliquid dispenser 200. In some embodiments, the robot 500 does notcontrol the motion of the liquid dispenser. In some embodiments, theliquid dispenser 200 and the robot 500 are coupled to a robotic gantry(not shown) that has three degrees of freedom. The degrees of freedomcan include movement in the X direction, Y direction, and rotation. InFIG. 58, the column 600 can connect to the robotic gantry (not shown).Any of the liquid dispensers described herein can be operably coupled toa robot 500. The manifolds 102, 202, 302, 402 can be coupled to arobotic arm of robot 500 which can move the manifold in space. Themotion of the robotic arm can have six degrees of freedom. For example,the robotic arm can include 1 degree of translational freedom, 2 degreesof translational freedom, 3 degrees of translational freedom, 1 degreeof rotational freedom, 2 degrees of rotational freedom, 3 degrees ofrotational freedom, or any combination of these.

FIGS. 61-64 show views of interior portions of some features of theliquid dispenser 300 described above. The pipette channel 310 can bedesigned to accommodate internal wiring and tubing. The pipette channel310 can include the tubes 360, 362 extending from the solenoid valve 358to the module 320. The pipette channel 310 can include a ribbon cable376 which transmits electrical signals and control signals. The ribboncable 376 can extend from the connector 366 to the module 320. The tubes360, 362, and the ribbon cable 376 can each include a bend 378. Thebends 378 are shown in a downward position in FIG. 61. The downwardposition of the bends 378 in the tubes 360, 362 and the ribbon cable 376corresponds to a downward position of the module 320. The bends 378 areshown in an upward position in FIG. 62. The upward position of the bends378 corresponds to an upward position of the module 320. As the module320 moves downward along the track 330 in the Z-direction, the bends 378in the tubes 360, 362 and the ribbon cable 376 move downward within thebase 332 of the pipette channel 310. The bends 378 can be accommodatedwithin a groove 380 in the base 332 of the pipette channel 310.

In some embodiments, movement in the Z-direction of the pipette tipengaged to the module 320 relative to the manifold 302 is controlled byfeatures housed in the pipette channel 310. The module 320 can includethe flange 326. The flange 326 can be fixedly attached to the coupling328. The coupling 328 is movable along the track 330. The movement ofthe coupling 328 in the Z-direction causes movement of the module 320 inthe Z-direction relative to the track 330. The movement of the coupling328 in the Z-direction causes movement of the module 320 in theZ-direction relative to the base 332 of the pipette channel 310.

The coupling 328 can include the nut 334. The nut 334 is configured tointeract with the ball screw 336. The nut 334 can include ball bearingswhich reduce friction when interacting with the ball screw 336. In otherembodiments, the nut 334 is threaded and interacts with a lead screw(not shown), rather than the ball screw 336 of this embodiment. The ballscrew 336 can be rotated with the motor 338. As the ball screw 336 isrotated, the coupling 328 translates along the ball screw 336. Thecoupling 328 is guided along the track 330 in the Z-direction. Rotationof the ball screw 336 in a first direction causes the coupling 328 totranslate downward in the Z-direction along the track 330. Rotation ofthe ball screw 336 in a second, opposite direction causes the coupling328 to translate upward in the Z-direction along the track 330.

Additional Features of Liquid Dispensers Described Herein

The liquid dispensers described herein can be configured to carry outpipetting operations in parallel, with each pipette channel actingindependently to aspirate and dispense liquid. Each pipette channel hasthe ability to move its corresponding pipette tip along the z-axis ofthe liquid dispenser independently of movement of another pipette tipmounted in the liquid dispenser. Thus, a liquid dispenser, as describedherein, is an assembly of pipette channels that together cooperate tocarry out such pipetting operations on solutions. The liquid dispenserthus, typically, can pick up and disengage pipette tips as needed, aswell as aspirate quantities of liquid up into, and dispense thosequantities of liquid from, such pipette tips. The motions and operationof the liquid dispenser is typically controlled by a processor such thatpipetting operations can be automated. Advantageously, the liquiddispenser can be configured to align pipette tips, e.g., with containersor cartridge inlet holes.

Advantageously, the liquid dispenser can be configured so that themodule circuit board, sensors (for example, but not limited to, sensorsto detect presence of pipette tips and sensors to detect force exertedon pipette tips during pipetting), the tip eject motor, the sleeve, thepipette tip and other items, move as a unit as the module, therebyminimizing the number of control lines that move across the instrumentduring use, reducing the likelihood that such control lines will becometangled during motion of the module, and increasing the likelihood thatthe module will remain in communication with other components that arefixed at various points within a preparatory or diagnostic apparatussuch as the base of the pipette channel and the manifold.

The layout of the components in the figures is for convenience only, andone of skill in the art would appreciate that other arrangements arepossible, depending upon environment and other factors. The electricalcomponents including the motors, pumps, and valves, can receiveinstructions from a processor (not shown). The processor can be locatedon the liquid dispenser or can be remote from the liquid dispenser.

Embodiments of liquid dispensers described herein can also include asensor configured to sense when vertical motion of the module isobstructed, and to provide a suitable signal directly to a processor(not shown), or indirectly (not shown) via printed circuit board. Thesensor can be mounted on the module or on another component of thepipette channel.

Optionally included within the liquid dispenser is a scanner (notshown). The scanner can be configured to read information (for example,but not limited to, sample and patient information), from one or more ofa container holding a liquid, a sample tube, a reagent holder, amicrofluidic cartridge, or any other container. The scanner can beelectrically connected directly (not shown) to a processor, orindirectly via a printed circuit board.

Embodiments of liquid dispensers described herein include pneumaticsolenoid valves, but other valves are contemplated. The valve can beassociated with each pipette channel, and serve to control operation ofeach module such as by, for example, controlling when to reducepressure, thereby causing a aspirating operation, or to increasepressure, thereby causing a dispense operation. Each valve is connectedto (including being in fluid communication with) the module via one ormore internal tubes which extend from the valve to the module.

The manifold of liquid dispensers described herein can be connected to apump (not shown) via an air-line or tubing (not shown) to the inletpressure port and inlet vacuum port. As described herein, the inletpressure port and inlet vacuum port are connected via one or morechannels and cross-channels in the manifold to ports in the pipettechannel. The ports in the pipette channel supply gas under pressure andgas under vacuum to a valve located within the pipette channel. Eachpipette channel contains an independently controllable solenoid valvethat selectively diverts air from the pump to the module associated withthe pipette channel, and therefore to a corresponding pipette tip.

Operation of liquid dispenser is typically controlled by one or morecircuit boards (PCB), including circuit board 164 within the module 120.The PCB additionally can receive electrical signals from electricalconnectors, including electrical connectors 170. Thus, the aspirate anddispense operations can be precisely controlled, by signals from thePCB, so that accurate volumetric control is achieved. In someembodiments, calibration of the liquid dispenser is required so that theamount of time to force or to aspirate gas that is required to dispenseor aspirate a desired volume of liquid is known. Thus, according to oneexample, the time between a valve opening and valve closing, ascontrolled by signals, is known and can be incorporated into the controlsoftware. The liquid dispense operations can be controlled by thehardware and software located within the liquid dispenser. In someembodiments, the liquid dispense operations can be controlled by thehardware and software located within the module 120.

The module 120 can include the second valve, as described herein. Themodule 120 can include a pump (not shown) and a motor (not shown)controlling its action. In some embodiments, the pump includes atranslating plunger controlled by a stepper motor, which receiveselectrical signals and/or control signals as input. The module 120 caninclude any hardware and/or software configured to complete aspirate anddispense operations.

The above-described embodiments have been provided by way of example,and the present disclosure is not limited to these examples. Multiplevariations and modifications to the disclosed embodiments will occur, tothe extent not mutually exclusive, to those skilled in the art uponconsideration of the foregoing description. Additionally, othercombinations, omissions, substitutions and modifications will beapparent to the skilled artisan in view of the disclosure herein.Accordingly, the present development is not intended to be limited bythe disclosed embodiments.

Embodiments of the pipette channel described herein are advantageouslymodular in design and thus compatible with any number of manifolds andmodules. In the illustrated embodiments, the manifold can include one ormore locations that accept a pipette channel. The locations on themanifold that accept a single pipette channel can be considered lanes.Each manifold can include one or more lanes (e.g., one lane, two lanes,three lanes, four lanes, five lanes, six lanes, a plurality of lanes,etc.). In some embodiments, the manifold includes two or more lanes. Insome embodiments, each lane is adjacent to another lane. In someembodiments, each lane is configured to accept a pipette channel in asingle orientation.

In some embodiments, each lane is configured to accept any pipettechannel of a plurality of pipette channels. As one example, the pipettechannel initially in one lane can be moved to another lane. In someembodiments, each lane is configured to accept a specific pipettechannel. As one example, a pipette channel configured to performaspirate and dispense operations only on reagents can be accepted into aspecific lane or one of a plurality of specific lanes of the manifold.The reagents may be aspirated and dispensed from tubes that only containreagents and do not contain sample swabs (such as a swab tip). Asanother example, a pipette channel configured to perform aspirate anddispense operations only on samples can be accepted into a specific laneor one of a plurality of specific lanes of the manifold. The samples maybe aspirated and dispensed from tubes that contain samples and sampleswabs (such as a swab tip). The ability to configure a manifold toaccept one type of pipette channel in a first lane (for example, apipette channel configured to aspirate and dispense fluids from reagenttubes) and to also accept a second, different type of pipette channel ina second lane (for example, a pipette channel configured to aspirate anddispense fluid from sample tubes) is particularly advantageous. In oneexample described in greater detail below, a pipette channel configuredto perform aspirate and dispense functions on fluids in reagent tubesrequire the associated pipette tip to be coupled to the tip adapter withless force than a pipette channel configured to perform aspirate anddispense functions on fluids in sample tubes.

In some embodiments, a lane can be defined by one or more structures onthe manifold. The lane can be defined by one or more openings configuredto accept fasteners of the pipette channel. The lane can be defined byone or more openings configured to accept pegs of the pipette channel.The lane can be defined by an electrical connector configured toelectrically connect to a corresponding electrical connector of apipette channel mated with the manifold. In some embodiments, the lanecan encompass only one electrical connector. The lane can be defined bythe pressure channel configured to pneumatically connect to acorresponding pressure cross-channel of a pipette channel mated with themanifold. In some embodiments, the lane can encompass only one pressurechannel. The lane can be defined by the vacuum channel configured topneumatically connect to a corresponding vacuum cross-channel of apipette channel mated with the manifold. In some embodiments, the lanecan encompass only one vacuum channel.

In some embodiments, a lane can be configured to accept one or morecomponents of the liquid dispenser. The lane can be defined by thelocation configured to accept a pipette channel. In some embodiments,each lane is configured to accept a single pipette channel. In someembodiments, a lane is configured to accept only one pipette channel.The lane can be defined by the location configured to accept a module.In some embodiments, each lane is configured to accept a single module.In some embodiments, a lane is configured to accept only one module.

In some embodiments, a lane and the one or more components of the liquiddispenser accepted thereon can be considered a unit. In someembodiments, a unit can be defined by function. The unit can be definedby the ability to perform aspirate and dispense operations. Two units ofa liquid dispenser can perform the same aspirate and dispense operationssimultaneously. Two units of a liquid dispenser can perform differentaspirate and dispense operations simultaneously. Two units of a liquiddispenser can perform the same aspirate and dispense operationssimultaneously. Two units of a liquid dispenser can independentlycontrol aspirate and dispense operations. Two units of a liquiddispenser can include two modules which independently perform aspirateand dispense operations. Two units of a liquid dispenser canindependently control movement in the Z-direction. Two units of a liquiddispenser can include two valves which can independently select betweenvacuum and pressure. In one example, a unit includes a lane of themanifold and a selectively receivable component received in the lane.The selectively receivable component can include a pipette channel, apipette module, a pipette channel coupled to a pipette module, or ablanking plate.

Advantageously, embodiments of the systems and methods described hereininclude the ability to control movements of the liquid dispenser, and insome cases to control movements of certain components the liquiddispenser independent of other components. In the illustratedembodiment, each pipette channel coupled to the manifold moves as a unitwith the manifold. In some embodiments, the manifold can move in theX-direction, along the width of the manifold. The movement of themanifold in the X-direction causes movement in the X-direction of eachpipette channel coupled to the manifold. In some embodiments, themanifold can move in the Y-direction, along the thickness of themanifold. The movement of the manifold in the Y-direction causesmovement in the Y-direction of each pipette channel coupled to themanifold. In some embodiments, the manifold can move in the Z-direction,along the height of the manifold. The movement of the manifold in theZ-direction causes movement in the Z-direction of each pipette channelcoupled to the manifold. In some embodiments, a pipette channel can movein the Z-direction independently of movement of the manifold. In someembodiments, a pipette channel coupled to the manifold can move in theZ-direction in the same direction as movement of the manifold. In someembodiments, a pipette channel coupled to the manifold can move in theZ-direction in the opposite direction as movement of the manifold.

In some embodiments, an advantage is the ability to mount the manifoldto any of a variety of gantry systems with no or very littlemodification of the manifold. In some embodiments, the manifold iscoupled to a gantry that is controlled by one or more belt drives. Insome embodiments, the gantry is controlled by one or more steppermotors. In some embodiments, the gantry is controlled by one or morelinear motors. In one example, a liquid dispenser system includes threemanifolds, each mounted on a separate rail configured to travel alongthe Y-axis of the system. In such embodiments, the linear motorsadvantageously allow the multiple manifolds mounted on separateY-direction rails to move along the same X-direction rail. In someembodiments, an advantage is that the linear motors allow threemanifolds mounted on three separate Y-direction rails to move along thesame X-direction rail.

In some embodiments, the pipette channel is calibrated for a specificfunction. In some embodiments, the pipette channel is configured inshape or design for a specific function. In some embodiments, thepipette channel is configured for a specific lane assignment. Thepipette channel can dictate the lane where the pipette channel isplaced. In some embodiments, two pipette channels coupled to a manifoldhave the same calibration settings. In some embodiments, two pipettechannels coupled to a manifold have different calibration settings. Insome embodiments, two pipette channels of two or more liquid dispensershave the same calibration settings. In some embodiments, two pipettechannels of two or more liquid dispensers have different calibrationsettings.

In some embodiments, an advantage is the ability to select between twopipette channels with different calibration settings related to volume.A manifold can include one pipette channel with a selected calibrationsetting, multiple pipette channels configured with the same selectedcalibration setting, or multiple pipette channels configured withdifferent selected calibration settings. As one example, a pipettechannel can include be calibrated to dispense smaller volumes thananother pipette channel mounted to the same manifold. As anotherexample, a pipette channel can be calibrated to dispense greater volumesthan another pipette channel mounted to the same manifold. In someembodiments, a pipette tip is mounted to a pipette channel configured todispense 1 mL of liquid. In some embodiments, a pipette tip is mountedto a pipette channel configured to dispense 5 mL of liquid. In someembodiments, a pipette tip is mounted to a pipette channel configured todispense between 0.5 mL and 1 mL of liquid. In some embodiments, apipette tip is mounted to a pipette channel configured to dispensebetween 1 mL and 5 mL of liquid. A plurality of pipette channels, eachindependently configured to dispense a particular volume, or range ofvolumes, can be selected and mounted to a manifold based on theparticular liquid dispensing requirements of the system in which themanifold is installed.

In some embodiments, an advantage is the ability to select between twopipette channels with different calibration settings related topressure. A manifold can include one pipette channel with a selectedcalibration setting, multiple pipette channels configured with the sameselected calibration setting, or multiple pipette channels configuredwith different selected calibration settings. In some embodiments, apipette tip is mounted to a pipette channel configured to dispense aliquid at 500 millibar. In some embodiments, a pipette tip is mounted toa pipette channel configured to dispense a liquid at between 250millibar and 750 millibar. In some embodiments, a pipette tip is mountedto a pipette channel configured to dispense a liquid at less than 750millibar. In some embodiments, a pipette tip is mounted to a pipettechannel configured to dispense a liquid at less than 500 millibar. Insome embodiments, a pipette tip is mounted to a pipette channelconfigured to dispense a liquid at less than 250 millibar. In someembodiments, the pressure is set by a pressure controller. The pressurecontroller can provide vacuum and pressure to the manifold. The pressurecontroller can provide instructions to control the vacuum and pressuresupplied to the manifold. In some embodiments, all pipette channelscoupled to a single manifold are provided with gas at the same pressure.For example, the system may include one pressure controller that feedsgas to the manifold, and all pipette channels coupled to the manifoldare provided with gas at the same pressure. The pressure controller canchange the pressure of the gas provided to all pipette channels coupledto the manifold.

FIGS. 65A-65B illustrate an embodiment of the manifold 600, the featuresof which can be used in combination with any manifold described herein.In some embodiments, the manifold 600 is designed to provide gas to afirst set of pipette channels coupled to a single manifold at a firstpressure and to simultaneously provide gas to a second, different set ofpipette channels coupled to the same single manifold at a second,different pressure. There are several ways to implement a manifoldconfigured to supply gas under varying pressure. For example, the systemcan include two or more separate pressure controllers simultaneouslyproviding gas at different pressures to the same single manifold. Otherconfigurations are possible. Instead of one pressure inlet and onevacuum inlet, there could be a plurality of pressure inlets and/or avariety of vacuum inlets. For example, in some embodiments, there aretwo pressure sources and two vacuum sources connected to correspondinginlets e.g., pressure inlet 602, pressure inlet 604, vacuum inlet 606,and vacuum inlet 608 of the manifold 600. Each pressure source isconnected to a single pressure channel and each vacuum source isconnected to a single vacuum channel, such that the manifold has twopressure channels 612, 614 and two vacuum channels 616, 618. Themanifold is split so the first pressure source and the first vacuumsource supply gas to a first set of lanes of the manifold. The secondpressure source and the second vacuum source supply gas to a second,different set of lanes of the manifold. The manifold can be divided invarious combinations. In some embodiments, the pipette channels thatreceive gas from the same pressure channel and the same vacuum pressurechannel are adjacent. The mating cross-channels, pressure cross-channel620 and vacuum cross-channel 622, for the vacuum and pressure channelscan be the same locations as other embodiments described herein. Thecross-channels 620, 622 can be in the same position regardless of thenumber or location of the pressure channels and vacuum channels locatedwithin the manifold.

In an alternative embodiment (not illustrated), the manifold includes afirst pressure channel that is physically and fluidically isolated froma second pressure channel, both of which are physically and fluidicallyisolated from a vacuum channel in the manifold. The valve of the pipettechannel is coupled to the first pressure channel, the second pressurechannel, and the vacuum channel and is designed to switch between thechannels to divert gas at a first pressure from the first pressurechannel, divert gas at a second, higher pressure from the secondpressure channel, or divert gas under vacuum to the dispense head. Insome embodiments, the valve of the pipette channel can be designed toswitch between two or more vacuum channels in the manifold. Thus, insome embodiments, the valve of the pipette channel can be designed toswitch between three or more channels supplying gas under pressureand/or gas under vacuum. In some embodiments, to allow each valve toswitch between three channels, the pipette channel includes two solenoidvalves in each pipette channel to distribute gas under pressure or gasunder vacuum. The options for three gas sources include, but are notlimited to, two pressure sources and one vacuum source; one pressuresource and two vacuum sources, etc. For two pressure sources and twovacuum sources, the pipette channel may include three solenoid valves ineach pipette channel to distribute gas under pressure or gas undervacuum. The manifold can be coupled to other types of pressure sourcesthat separately supply gas under pressure and gas under vacuum to thevalves in two or more pipette channels. A plurality of pipette channels,each independently configured to dispense a liquid at a differentpressure, or range of pressures, can be selected and mounted to amanifold based on the particular liquid dispensing requirements of thesystem in which the manifold is installed.

In some embodiments, an advantage is the ability to select between twopipette channels with different calibration settings related to speed. Amanifold can include one pipette channel with a selected calibrationsetting, multiple pipette channels configured with the same selectedcalibration setting, or multiple pipette channels configured withdifferent selected calibration settings. As one example, a pipettechannel can include a calibration for faster aspirate and dispenseoperations than another pipette channel, such as for high speedoperations. As one example, a pipette channel can include a calibrationfor slower aspirate and dispense operations than another pipettechannel.

In some embodiments, an advantage is the ability to select between twopipette channels with different calibration settings related to force. Amanifold can include one pipette channel with a selected calibrationsetting, multiple pipette channels configured with the same selectedcalibration setting, or multiple pipette channels configured withdifferent selected calibration settings. As one example, a pipettechannel can be calibrated to engage or disengage a pipette tip withgreater force than another pipette channel mounted to the same manifold.In one non-limiting implementation, a first pipette channel thatinteracts with one or more samples is configured to engage a pipette tipwith greater force to prevent inadvertent disengagement of the pipettetip from the tip adapter by swabs within a sample tube. In anothernon-limiting example, a second pipette channel that interacts withreagents in reagent tubes is configured to engage a pipette tip withlesser force than the first pipette channel, because the second pipettechannel will not interact with objects in a reagent tube that mayinadvertently disengage the pipette tip, such as a sample swab.

In some embodiments, an advantage is the ability to select between twopipette channels with different configurations. As one example, the twopipette tips can have different configurations related to differentlysized pipette tip adapters. A manifold can include one pipette channelwith a selected calibration setting, multiple pipette channelsconfigured with the same selected calibration setting, or multiplepipette channels configured with different selected calibrationsettings. In some embodiments, two pipette channels can includedifferent tip adapters. As one example, a pipette channel can include alarger tip adapter for a larger pipette tip than another pipettechannel. As another example, a pipette channel can include more featuresthan another, lower cost pipette channel. As another example, the twopipette channels can have a different configuration of the pipettemodule, for example, as shown in FIG. 35 where the pipette module 320 ismounted adjacent to a side 316 of the pipette channel 310 along theX-axis of the liquid dispenser 300.

In some embodiments, an advantage is the ability to design a liquiddispenser configured to accept two or more pipette channels that havedifferent features, such as but not limited to different calibrationsettings or configurations. In some embodiments, the two or moredifferent pipette channels can have the same configuration of electricalconnectors designed to mate with the electrical connectors of themanifold. In some embodiments, the two or more different pipettechannels can have the same configuration of pneumatic connections. Insome embodiments, the two or more different pipette channels can haveone or more different dimensions (e.g., height, thickness, width). Insome embodiments, the two or more different pipette channels can havedifferent modules. In some embodiments, the two or more differentpipette channels can accept differently sized pipette tips. In someembodiments, the two or more different pipette channels can havedifferent tip adapters. In some embodiments, the two or more differentpipette channels can be calibrated to dispense fluids in different ways,such as but not limited to calibrated to dispense different volumes offluid or calibrated to dispense fluid at different pressures. In someembodiments, two or more different pipette channels are configured to beaccepted on any lane of the manifold.

In some embodiments, an advantage is the ability to design a manifoldincluding two or more different lanes wherein each lane is configured toaccept pipette channels that are the same. In some embodiments, the twoor more different lanes can have the same configuration of electricalconnectors within the lane. In some embodiments, the two or moredifferent lanes can have the same configuration of pneumatic connection.In some embodiments, the two or more different lanes can have one ormore different dimensions (e.g., height, thickness, width). In someembodiments, an advantage is the ability to design a manifold includingtwo or more different lanes wherein each lane is configured to accept apipette channel that is different from pipette channels mounted in otherlanes.

In some embodiments, an advantage is the ability to design a systemincluding two or more different liquid dispensers with differentmanifolds, the different manifolds having certain features in common andcertain features which are different. In one example, one lane of eachof the two or more different manifolds can have the same configurationof electrical connectors within the lane. In another example, one laneof each of the two or more different manifolds can have the sameconfiguration of pneumatic connections. In some embodiments, one lane ofeach of the two or more different manifolds in the same system can haveone or more different dimensions (e.g., height, thickness, width).

In some embodiments, an advantage is the ability to design a manifoldconfigured to accept a specific number of pipette channels. In oneimplementation, the liquid dispenser includes one pipette channel but isconfigured to include more than one pipette channel. In anotherimplementation, the liquid dispenser is configured to include only onepipette channel. In another implementation, the liquid dispenserincludes three pipette channels but is configured to include more thanthree pipette channels. In another implementation, the liquid dispenseris configured to include only three pipette channels. In yet anotherimplementation, the liquid dispenser includes five pipette channels butis configured to include more than five pipette channels. In anotherimplementation, the liquid dispenser is configured to include only fivepipette channels.

In some embodiments, an advantage is the ability to control the flow ofa gas with a valve within a pipette channel. In the illustratedembodiments, a pipette channel includes an individually-actuatablesolenoid valve. In some embodiments, the solenoid valve is a lowpressure solenoid valve. In some embodiments, the solenoid valve israted for less than 30 psi. In some embodiments, the solenoid valve israted for less than 20 psi. In some embodiments, the solenoid valve israted for less than 10 psi. In some embodiments, the solenoid valve israted for between 5 and 10 psi. In some embodiments, the solenoid valveis rated for between 1 and 15 psi. In some embodiments, the solenoidvalve is rated for between 1 and 20 psi. In some embodiments, thesolenoid valve is optimized for low pressure applications. In someembodiments, the solenoid valve includes a diaphragm seal. In someembodiments, the solenoid valve includes a flexible seal. In theillustrated embodiments, the solenoid valve is located within a housingof the pipette channel. The solenoid valve is configured to control theflow of a gas from the manifold to the module of the pipette channel.The solenoid valve acts as a selector between vacuum and pressure.

In some embodiments, an advantage is the ability to control aspirate anddispense operations within a pipette channel. In some embodiments, amodule of the pipette channel can include a second valve configured tocontrol the aspirate and dispense operations. The second valve usespressure and vacuum from the solenoid valve of the pipette channel tocontrol the aspirate or dispense operations. Advantageously, in somesystems described herein, each module mounted in a single manifold hassimultaneous access to pressure. In some systems described herein, eachmodule mounted has simultaneous access to vacuum. In some embodiments,each pipette channel includes an independent air-line that connects themodule to the solenoid valve of the pipette channel. The air-linesdescribed herein can accept any suitable gas, such as but not limited toatmospheric air or nitrogen. In the illustrated embodiment, anindependent line that connects the module to the solenoid valve isenclosed within the housing of the pipette channel. In some embodiments,the independent line supplies both pressure and vacuum from the manifoldto the module.

In some embodiments, an advantage is that each module includes anindependent coupling to the manifold. In the illustrated embodiment,each pipette channel includes a single module. In the illustratedembodiment, each module is coupled to a single lane of the manifold. Asdescribed herein, each lane can include an independent electricalconnection for the module. As described herein, each lane can include anindependent pneumatic connection for the module.

In some embodiments, an advantage is the ability to have a system thatcan be tailored for a particular process. Systems described herein canbe tailored for the demands of a laboratory. As one example, the systemcan be tailored based on the number of liquid dispensers employed. Insome embodiments, a system can include one liquid dispenser, two liquiddispensers, three liquid dispensers, four liquid dispensers, five liquiddispensers, six liquid dispensers, seven liquid dispensers, eight liquiddispensers, nine liquid dispensers, ten liquid dispensers, etc. In someembodiments, each liquid dispenser includes a single manifold. In someembodiment, each manifold includes one or more pipette channels. In someembodiments, each pipette channel includes a single pipette module.

Systems described herein can be advantageously designed by a user thatselects the number of liquid dispensers and the number of pipettechannels. Two liquid dispensers of the system can have the same numberof pipette channels (e.g., a system including two liquid dispensers eachhaving one pipette channel, a system including two liquid dispenserseach having two pipette channels, a system including two liquiddispensers each having three pipette channels, a system including twoliquid dispensers each having four pipette channels, or a systemincluding two liquid dispensers each having five pipette channels,etc.). Two liquid dispensers of the system can have a different numberof pipette channels (e.g., a system including a liquid dispenser withone pipette channel in combination with a liquid dispenser with twopipette channels, three pipette channels, four pipette channels, or fivepipette channels; a system including a liquid dispenser with two pipettechannels in combination with a liquid dispenser with three pipettechannels, four pipette channels, or five pipette channels; a systemincluding a liquid dispenser with three pipette channels in combinationwith a liquid dispenser with four pipette channels or five pipettechannels, a system including a liquid dispenser with four pipettechannels in combination with a liquid dispenser with five pipettechannels, etc.)

In some embodiments, an advantage is the ability to have two or moreliquid dispensers of a system perform the same function. In some methodsof use, two or more liquid dispensers of a system can receiveinstructions from a processor. The two or more liquid dispensers of asystem can receive the same instructions to perform the same method. Asone example, the two or more liquid dispensers can move in the samepattern of movements. As one example, the two or more liquid dispenserscan perform the same method over the same period of time. As oneexample, one or more pipette channels of the two or more liquiddispensers can perform the same aspirate and dispense operations.

In some implementations, an advantage is the ability to have two or moreliquid dispensers of a system perform different functions. Two or moreliquid dispensers of a system can receive instructions from a processor.The two or more liquid dispensers of the system can receive differentinstructions to perform different methods. As one example, one liquiddispenser of a system can interact with one or more biological samplesof one or more patients contained in sample tubes. Another liquiddispenser of the system can interact with one or more reagents containedin reagent tubes. The two or more liquid dispensers of the system caninclude different calibration settings, as described herein. As oneexample, the liquid dispenser of the system that interacts with one ormore biological samples may be calibrated to require a greater force toengage and disengage pipette tips than the liquid dispenser of thesystem that interacts with one or more reagents. An advantage is thatthe greater force may reduce the disengagement of pipette tips due toswabs within the sample tubes. In some embodiments, the pipette channelthat interacts with one or more biological samples may require at least5 pounds of force to engage or disengage a pipette tip to a tip adapter.In some embodiments, the pipette channel that interacts with one or morebiological samples may require at least 10 pounds of force to engage ordisengage a pipette tip to a tip adapter. In some embodiments, thepipette channel that interacts with one or more reagents contained inreagent tubes may require less than 5 pounds of force to engage ordisengage a pipette tip to a tip adapter. In some embodiments, thepipette channel that interacts with one or more reagents contained inreagent tubes may require less than 10 pounds of force to engage ordisengage a pipette tip to a tip adapter.

Liquid dispensers described herein can be advantageously tailored for aparticular process. In some embodiments, two pipette channels coupled toa manifold are similar or identical. As one example, two or more pipettechannels of a liquid dispenser can perform the function (e.g., bothpipette channels interact with one or more samples in sample tubes, bothpipette channels interact with one or more reagents in reagent tubes,etc.). As another example, two or more pipette channels of a liquiddispenser can have the same shape or configuration. As a furtherexample, two or more pipette channels of a liquid dispenser can have thesame calibration settings.

In some embodiments, two pipette channels coupled to a manifold havedifferent features. As one example, two or more pipette channels of aliquid dispenser can perform different functions (e.g., a pipettechannel interacts with one or more samples in sample tubes and a pipettechannel coupled to the same manifold interacts with one or more reagentsin reagent tubes). As another example, two or more pipette channels of aliquid dispenser can be configured with different calibration settings.The pipette channel that interacts with one or more biological samplesin sample tubes may be calibrated to engage and disengage pipette tipswith a greater force than the pipette channel of the liquid dispenserthat interacts with one or more reagents in reagent tubes. As a furtherexample, two or more pipette channels of a liquid dispenser can have adifferent shape or configuration. As still another example, a liquiddispenser can have mixed-purpose pipette channels.

Processors in systems described herein can send instructions related tothe pipette channel and the lane. In some embodiments, the processorsends instructions to each lane, and the components coupled to the lane,independently of instructions sent to another lane of the manifold. Insome embodiments, the processor sends instructions to two or more lanes,and the components coupled to the two or more lanes, simultaneously. Insome embodiments, the system may require identification of each pipettechannel mounted to the manifold. In some embodiments, the system mayrequire identification of each pipette channel mounted to the manifoldand the corresponding lane in which each pipette channel is mounted.

In some embodiments, the processor sends instructions that direct theone or more pipette channels coupled to a manifold to transfer a samplefrom a container to another container. In some embodiments, theinstructions employ a pipette channel of one or more pipette channels ofa liquid dispenser to transfer a reagent from a container to anothercontainer. The instructions can include instructions to: employ thepipette channel to transfer a sample from a sample container to areagent holder; employ the pipette channel to transfer a sample from asample container to a microfluidic network; employ the pipette channelto direct a sample from the sample container to one or more additionalcontainers; contact the pipette tip to a sample; contact the pipette tipto a reagent; to place the pipette tip in a container; to disengage ordiscard a used pipette tip and to engage an unused pipette tip. Invarious embodiments, a computer program product includes computerreadable instructions thereon for operating one or more liquiddispensers. In some embodiments, a computer program product includescomputer readable instructions thereon for causing the system to performvarious aspirate and dispense operations.

Liquid dispensers described herein can recognize a pipette channelcoupled to the manifold. In some embodiments, an advantage is theability of a liquid dispenser to perform verification and validation ofa pipette channel coupled to the manifold. In some embodiments, anadvantage is the ability of a liquid dispenser to direct instructions toa single pipette channel of two or more pipette channels based oninformation obtained during a verification and validation process. Insome embodiments, an advantage is the ability of a liquid dispenser torecognize which lane(s) of the manifold has a pipette channel mounted inthe lane. In some embodiments, an advantage is the ability of a liquiddispenser to direct instructions to a lane of two or more lanes based oninformation about which lane(s) have a pipette channel mounted in thelane.

Liquid dispensers described herein advantageously reduce machine downtime. Down time may require the system to stop operating and be powereddown. The system may be powered down for any number of reasons,including but not limited to the liquid dispenser (or a component of theliquid dispenser) not operating properly; routine maintenance; to changea pipette channel mounted to the manifold to a pipette channel havingdifferent features; or to change a calibration setting of a pipettechannel already mounted to the manifold. As one example, replacing onepipette channel of a liquid dispenser described herein can take lessthan one minute. In some methods of use, replacing one pipette channelof a liquid dispenser can take less than five minutes. In some methodsof use, replacing one pipette channel of a liquid dispenser can takeless than three minutes. In contrast, replacing a dispense head in atraditional liquid dispenser may include connecting and disconnectingpneumatic connections, connecting and disconnecting electricalconnections, and/or connecting and disconnecting hardware connections.Replacing a dispense head in a traditional liquid dispenser can takeover an hour. An advantage is a reduction in machine down time by over95%. In some embodiments, the liquid dispenser described herein isconfigured to be operational 24 hours a day, seven days a week. In someembodiments, the liquid dispenser described herein is configured to berapidly repaired in order to be operational nearly 24 hours a day, sevendays a week.

In some embodiments, the method of replacing one pipette channel caninclude the step of unscrewing one or more fasteners. In someembodiments, the fasteners are two screws. In some embodiments, the twoscrews are captive screws. An advantage is that the screws remain withthe pipette channel which prevents loss of the screws. An advantage isthat the screws remain with the pipette channel which prevents use ofthe incorrect hardware. An advantage is that the captive screws increasethe speed in which the pipette channel can be replaced. In someembodiments, the method of replacing one pipette channel can include thestep of pulling the pipette channel away from the manifold. In someembodiments, the method of replacing one pipette channel can include thestep of disengaging one or more pegs of the pipette channel from themanifold.

In some embodiments, the method of replacing one pipette channel caninclude the step of aligning one or more pegs of the replacement pipettechannel with the manifold. In some embodiments, one or more pegs includetwo pegs. In some embodiments, one or more pegs engage correspondingopenings in the manifold. In some embodiments, aligning one or more pegsof the replacement pipette channel also aligns one or more electricalconnectors of the pipette channel with one or more electrical connectorsof the manifold. In some embodiments, the one or more pegs extend beyondthe electrical connectors of the pipette channel in the y-axisdirection. As one example, see FIG. 47. An advantage is that the pegs ofthe pipette channel engage the manifold before the electrical connectorsof the pipette channel engage the manifold. An advantage is that the oneor more pegs may prevent damage to the electrical connectors. In someembodiments, aligning one or more pegs of the replacement pipettechannel aligns one or more pneumatic connections of the pipette channelwith the manifold. In some embodiments, aligning one or more pegs of thereplacement pipette channel aligns the pressure channel of the manifoldwithin the pressure cross-channel of the pipette channel. In someembodiments, aligning one or more pegs of the replacement pipettechannel aligns the vacuum channel of the manifold within the vacuumcross-channel of the pipette channel. In some embodiments, the method ofreplacing one pipette channel can include the step of pushing thepipette channel toward the manifold. In some embodiments, the method ofreplacing one pipette channel can include the step of screwing twoscrews. In some embodiments, the step of screwing two screws alsoincludes compressing two or more o-rings. An advantage is that an o-ringincreases the seal between the pressure channel of the manifold and thepressure cross-channel of the pipette channel. An advantage is that ano-ring increases the seal between the vacuum channel of the manifold andthe vacuum cross-channel of the pipette channel.

Embodiments of liquid dispensers described herein advantageously allowfeatures in one lane of the manifold to be blocked when that lane is notin use. In some embodiments, a blanking plate can be installed in a laneof the manifold to block, or seal, features in the lane when a pipettechannel is not mounted in the lane. The blanking plate can include oneor more pegs. The blanking plate can include one or more screws. Theblanking plate can cover the pneumatic connections of a lane, therebyclosing off or sealing the pneumatic connections. The blanking plate cancover the one or more electrical connectors of the lane. An advantage isthat the blanking plate can prevent damage to features in a lane whenthey are not in use. In some methods of use, the blanking plate isinstalled for prototyping. In some methods of use, the blanking plate isinstalled for troubleshooting. In some methods of use, the blankingplate can be installed to determine whether other lanes of the manifoldare in operation. In some methods of use, one or more blanking platescan be installed to isolate a lane.

Systems described herein enable a liquid dispenser to be easily andquickly reconfigured. As one example, the liquid dispenser can bereconfigured if one or more pipette channels become inoperable. In someembodiments, one or more pipette channels can be replaced with ablanking plate. The blanking plate can limit the loss of pressure fromthe pressure channel of the manifold. The blanking plate can limit theloss of vacuum from the vacuum channel of the manifold. The blankingplate can enable operation of the liquid dispenser with the one or moreremaining pipette channels.

In some embodiments, an advantage is the ability to rearrange theremaining pipette channels with respect to the manifold. In someembodiments, two or more pipette channels perform different functions.An advantage is that the user can remove a pipette channel performing afunction and replace the pipette channel with a blanking plate. Anadvantage is that the user can move a pipette channel performing a firstfunction to another location, such as another lane, of the manifold toperform a second, different function.

In some embodiments of pipette channels described herein, o-rings arecaptive. An advantage is that the o-rings remain with the pipettechannel which prevents loss of the o-rings. Another advantage is thatthe o-rings remain with the pipette channel which prevents use ofincorrectly sized o-rings. Captive o-rings can also increase the speedin which the pipette channel can be replaced. In some embodiments, thepipette channel includes a dove-tail o-ring groove. In someimplementations, the opening of the o-ring groove is smaller in diameterthan the o-ring. In some embodiments, the opening of the o-ring grooveincludes one or more tapered projections that interlock with the largerdiameter of the o-ring once the o-ring is within the o-ring groove.

Systems described herein substantially reduce the likelihood ofincorrectly connecting the electrical connectors between the pipettechannel and the manifold, reducing the risk of damage to the electricalconnectors. In the illustrated embodiments, the electrical connector ofthe pipette channel is automatically aligned with the electricalconnector of the manifold when the pegs of the pipette channel arealigned.

In some embodiments, an advantage is the ability to substantially reducethe likelihood of incorrectly connecting pipette channels to electricalsources. In the illustrated embodiments, the manifold is connected toone or more outside sources (e.g., Ethernet connector, power connector,pipettor communication connector). In the illustrated embodiments, oneor more pipette channels are connected to the outside sources via themanifold. In the illustrated embodiments, the manifold includes aninternal system to distribute these connections to each of the pipettechannels. In contrast, a traditional liquid dispenser may includeseparate electrical sources for each dispense head or pipettor. Forinstance, a traditional liquid dispenser having five pipettors may havefive or more separate electrical sources. During installation or repair,these separate electrical sources may be connected to the incorrectpipettor or not connected to any pipettor. An advantage is reducing thelikelihood of incorrectly connecting electrical sources to one or morepipette channels.

In some embodiments, an advantage is the ability to substantially reducethe likelihood of incorrectly connecting the pneumatic connectionsbetween the pipette channel and the manifold. In the illustratedembodiments, the pneumatic connections of the pipette channel areautomatically aligned with the manifold when the pegs of the pipettechannel are aligned. In the illustrated embodiments, the pressurecross-channel of the pipette channel is automatically aligned with thepressure channel of the manifold when the pegs of the pipette channelare aligned. In the illustrated embodiments, the vacuum cross-channel ofthe pipette channel is automatically aligned with the vacuum channel ofthe manifold when the pegs of the pipette channel are aligned.

In some embodiments, an advantage is the ability to substantially reducethe likelihood of incorrectly connecting the pneumatic sources. In theillustrated embodiments, the manifold is connected to one or moreoutside gas sources (e.g., via the inlet pressure port and the inletvacuum port). In the illustrated embodiments, one or more pipettechannels are connected to pressure and vacuum via the manifold. In theillustrated embodiments, the manifold includes an internal system ofchannels to distribute pressure and vacuum to each of the pipettechannels. In contrast, a traditional liquid dispenser may includeseparate pneumatic sources independently connected to each dispense heador pipettor. For instance, a traditional liquid dispenser having fivepipettors may have five separate pressure sources and/or five separatevacuum sources. During installation or repair, these separate pneumaticsources may be connected to the incorrect pipettor or not connected toany pipettor. An advantage is reducing the likelihood of incorrectlyconnecting pneumatic sources to one or more pipette channels.

Systems described herein advantageously allow an assembled, modularpipette channel to be supplied to an end user. In the illustratedembodiment, the pipette channel encloses a solenoid valve that controlswhether gas under pressure or gas under vacuum is supplied to the moduleof a pipette channel. In the illustrated embodiment, the pipette channelencloses a secondary valve, such as a solenoid valve, to controlaspirate and dispense operations within the module. In some embodiments,an advantage is the ability to return an assembled, modular pipettechannel to the manufacturer. Advantageously, systems described hereininclude the ability to troubleshoot a malfunctioning or inoperativepipette channel apart from the manifold. In some cases, troubleshootingcan be performed on a pipette channel that has been removed from themanifold, while the remaining pipette channels mounted to the manifoldcontinue aspirate and dispense operations. In one non-limiting example,a malfunctioning or inoperative pipette channel is disengaged from themanifold in one minute or less, and a new pipette channel (or a blankingplate) is installed in the now-vacated lane of the manifold in oneminute or less. Accordingly, in some implementations of systemsdescribed herein, a liquid dispenser can experience two minutes or lessof downtime to replace a malfunctioning or inoperative pipette channel.

1-58. (canceled)
 59. A method of dispensing and aspirating a fluidcomprising: providing a manifold comprising a vacuum channel and apressure channel; providing one or more pipette channels, each pipettechannel comprising a dispense head, a vacuum port, a pressure port, andan independently controlled valve in simultaneous fluid communicationwith the vacuum port and the pressure port; selectively engaging the oneor more pipette channels to the manifold, wherein selectively engagingcomprises connecting each vacuum port of the one or more pipettechannels to the vacuum channel of the manifold and connecting eachpressure port of the one or more pipette channels to the pressurechannel of the manifold; transmitting control signals from the manifoldto a first pipette channel of the one or more pipette channels toindependently control operation of the independently controlled valve toselectively direct gas under vacuum or gas under pressure receivedthrough the vacuum port and the pressure port of the first pipettechannel to the dispense head of the first pipette channel; andperforming aspirate and dispense operations with the first pipettechannel, the aspirate and dispense operations comprising aspirating thefluid or dispensing the fluid in response to receipt of gas under vacuumor gas under pressure, respectively, in the dispense head of the firstpipette channel from the independently controlled valve of the firstpipette channel.
 60. The method of claim 59, furthering comprisingselectively engaging the first pipette channel and a second pipettechannel to the manifold, and wherein the method further comprises:transmitting control signals from the manifold to the second pipettechannel to independently control operation of the independentlycontrolled valve to selectively direct gas under vacuum or gas underpressure received through the vacuum port and the pressure port of thesecond pipette channel to the dispense head of the second pipettechannel; and performing aspirate and dispense operations with the secondpipette channel, the aspirate and dispense operations comprisingaspirating a second fluid or dispensing a second fluid in response toreceipt of gas under vacuum or gas under pressure, respectively, in thedispense head of the second pipette channel from the independentlycontrolled valve of the second pipette channel.
 61. The method of claim60, wherein the aspirate and dispense operations of the first pipettechannel and the second pipette channel occur simultaneously.
 62. Themethod of claim 60, wherein the aspirate and dispense operations of thefirst pipette channel and the second pipette channel occurindependently.
 63. The method of claim 60, wherein the first pipettechannel dispenses at the same time the second pipette channel aspirates.64. The method of claim 60, wherein the first pipette channel and thesecond pipette channel simultaneously aspirate a different volume offluid.
 65. The method of claim 60, wherein the first pipette channel andthe second channel simultaneously dispense a different volume of liquid.66. The method of claim 60, wherein the first pipette channel and thesecond pipette channel simultaneously aspirate a volume of fluid atdifferent pressures.
 67. The method of claim 60, wherein the firstpipette channel and the second channel simultaneously dispense a volumeof fluid at different pressures.
 68. The method of claim 60, wherein theindependently controlled valve of the first pipette channel diverts gasunder pressure at the same time the independently controlled valve ofthe second pipette channel diverts gas under vacuum.
 69. The method ofclaim 60, wherein the independently controlled valve of the firstpipette channel starts or stops the diversion of gas independently ofthe independently controlled valve of the second pipette channel. 70.The method of claim 59, furthering comprising selectively engaging thefirst pipette channel and a second pipette channel to the manifold,wherein the valve of the first pipette channel diverts gas underpressure to the dispense head of the first pipette channel at the sametime the valve of the second pipette channel diverts gas under vacuum tothe dispense head of the second pipette channel, such that the dispensehead of the first pipette channel dispenses a fluid at the same time thedispense head of the second pipette channel aspirates a fluid.
 71. Themethod of claim 59, wherein the pressure channel comprises a pluralityof pressure cross-channels and the vacuum channel comprises a pluralityof vacuum cross-channels, and wherein each pipette channel is configuredto connect to one pressure cross-channel and one vacuum cross-channelwhen the pipette channel is selectively engaged to the manifold.
 72. Themethod of claim 71, wherein the manifold comprises a plurality of lanes,each lane comprising one pressure cross-channel and one vacuum crosschannel, and wherein selectively engaging comprises engaging one pipettechannel to any one lane of the plurality of lanes.
 73. The method ofclaim 59, further comprising, in sequence, aspirating the fluid inresponse to receipt of gas under vacuum in the dispense head of thefirst pipette channel and dispensing the fluid in response to receipt ofgas under pressure in the dispense head.
 74. The method of claim 59,further comprising coupling a single source of gas under pressure and asingle source of gas under vacuum to the manifold.
 75. The method ofclaim 59, wherein the pressure channel terminates at an inlet pressureport and the vacuum channel terminates at an inlet vacuum port, whereinthe manifold only accepts gas under pressure and gas under vacuumthrough the inlet pressure port and the inlet vacuum port, respectively.76. The method of claim 59, wherein the pipette channel only accepts gasunder pressure and gas under vacuum through the pressure port and thevacuum port, respectively.
 77. The method of claim 59, furthercomprising transmitting electrical signals from the manifold to the oneor more pipette channels, each pipette channel powered independently ofany pipette channel by the electrical signals transmitted from themanifold.
 78. The method of claim 77, wherein each of the one or morepipette channels only receives control signals and electrical signalsthrough the electrical connection with the manifold.
 79. The method ofclaim 59, further comprising reducing free-fall of the dispense head inthe event of loss of electrical signals via a magnetic brake.
 80. Themethod of claim 59, wherein selectively engaging the first pipettechannel with the manifold comprises aligning one or more pegs of thepipette channel with one or more openings of the manifold.
 81. Themethod of claim 59, wherein selectively engaging the first pipettechannel with the manifold comprises tightening one or more captivescrews of the pipette channel.
 82. The method of claim 59, whereinselectively engaging the first pipette channel with the manifoldcomprises compressing a seal between the first pipette channel and themanifold.
 83. The method of claim 82, wherein the seal is a captiveo-ring of the pipette channel.
 84. The method of claim 59, furthercomprising selectively directing gas under pressure and gas under vacuumreceived through the pressure port and the vacuum port of the firstpipette channel to the dispense head of the first pipette channel via atube.
 85. The method of claim 84, wherein the tube is the only pneumaticconnection between the valve and the dispense head.
 86. The method ofclaim 84, wherein the tube is configured to bend as the dispense headmoves vertically.
 87. The method of claim 59, wherein the fluidcomprises a liquid.
 88. The method of claim 59, wherein the fluidcomprises a gas. 89-170. (canceled)